CARDIAC NEXT-GENERATION SEQUENCING PANELS · Duchenne muscular dystrophy disease (DMD) will only be...
Transcript of CARDIAC NEXT-GENERATION SEQUENCING PANELS · Duchenne muscular dystrophy disease (DMD) will only be...
CARDIAC NEXT-GENERATION SEQUENCING PANELS
Mail: One Gustave L. Levy Place, Box 1497 1 CLIA #: 33D2097541 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25 T: 800-298-6470 New York, NY 10029 F: 212-241-0139 www.sema4.com
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25 New York, NY 10029
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TABLE OF CONTENTS
GENETIC TESTING FOR INHERITED CARDIOVASCULAR CONDITIONS 6
GENETICS AND INDICATIONS 6
TESTING METHODS, SENSITIVITY, AND LIMITATIONS 7
TURNAROUND TIME 9
SPECIMEN AND SHIPPING REQUIREMENTS 9
CUSTOMER SERVICES AND GENETIC COUNSELING 10
THE COMPREHENSIVE CARDIOMYOPATHY PANEL 11
DILATED CARDIOMYOPATHY (DCM) SUBPANEL 23
ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY (ARVC) SUBPANEL 28
HYPERTROPHIC CARDIOMYOPATHY (HCM) SUBPANEL 30
LEFT VENTRICULAR NON-COMPACTION CARDIOMYOPATHY (LVNC) SUBPANEL 33
THE COMPREHENSIVE ARRHYTHMIAS PANEL 35
BRUGADA SYNDROME (BRS) SUBPANEL 40
CATECHOLAMINERGIC POLYMORPHIC VENTRICULAR TACHYCARDIA (CPVT) SUBPANEL 42
LONG / SHORT QT SYNDROME (LQTS / SQTS) SUBPANEL 44
AORTOPATHIES PANEL 46
CONGENITAL HEART DISEASE (CHD) PANEL 49
FAMILIAL HYPERCHOLESTEROLEMIA (FH) PANEL 52
PULMONARY HYPERTENSION (PAH) PANEL 54
METABOLIC CARDIOMYOPATHY PANEL 55
NOONAN SPECTRUM DISORDERS PANEL 57
HEREDITARY HEMORRHAGIC TELANGIECTASIA PANEL 59
REFERENCES 60
DISCLAIMER 69
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Genetic Testing for INHERITED CARDIOVASCULAR CONDITIONS
Many cardiovascular diseases have a genetic background and can be inherited from parents to their offspring. Controlling for risk factors such as smoking, hypertension, high cholesterol, and diabetes, researchers have established genetic etiology’s significant contribution in cardiovascular disease through twin studies and investigations of families with early onset cardiac complications. For example, a monozygotic twin has a marked increase in risk of early cardiovascular mortality when the first twin has died due to cardiac complications. This in turn supports genetic testing of families in order to identify changes in genes and pathways whose altered functions affect cardiovascular outcomes. Further, genetic testing can improve diagnostic accuracy and refine family management by identifying the molecular etiology of disease.
Next-generation sequencing (NGS) technology is ideal for diagnostic testing of families and index cases with cardiovascular complications due to the extreme locus heterogeneity and phenotypic overlap between the genes involved. Sema4 utilizes Agilent SureSelectQXT target enrichment library prep with Illumina NovaSeq sequencing to detect pathogenic variants in genes involved in cardiovascular disease. A comprehensive menu of heritable cardiovascular conditions was curated by experts and relevant genes were selected based on literature review, clinical actionability scores, and comparison with commercially available assays. The Cardiac Panel includes 241 genes with the following subpanels: Comprehensive Cardiomyopathy (190), Dilated Cardiomyopathy (DCM; 57), Hypertrophic Cardiomyopathy (HCM; 40), Left Ventricular Non-Compaction Cardiomyopathy (LVNC; 20), Comprehensive Arrhythmias (54), Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC; 8), Brugada Syndrome (BrS; 20), Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT; 8), Long / Short QT Syndrome (19), Aortopathies (33), Congenital Heart Disease (CHD; 44), Familial Hypercholesterolemia (FH; 4), Pulmonary Hypertension (10), Metabolic Cardiomyopathy (24), Noonan Spectrum Disorders (19), and Hereditary Hemorrhagic Telangiectasia Panel (5).
Customizable testing of the cardiac panel is available along with targeted familial testing. Genetic testing can help clarify the underlying cause of a cardiac complication, provide information on the likelihood of related health issues, and establish risk to other family members and future generations.
Genetics
The disorders included in this panel may be inherited in an autosomal dominant (AD), autosomal recessive (AR), X-linked (XL), or isolated cases (IC) manner. For genes displaying an AD mode of inheritance, an affected parent carrying the mutated gene has a 50% chance of passing the variant on to an offspring, regardless of gender. Some of these genes are not fully penetrant, meaning that an individual may have a mutated gene but not display any of the signs/symptoms of the disorder. Additionally, these disorders may have variable expressivity indicating that individuals carrying the same pathogenic variant may display differing features and/or differing severity. For diseases with AR inheritance, the risk for a couple who are both carriers to have a child affected with the disease is 25% for each pregnancy. The parents of an affected child are most often obligate carriers (heterozygotes) and each carry one mutant allele (unless a de novo mutation occurs). An X-linked inheritance means that the risk of a male offspring with the disorder will be 50% if the mother carries an XL mutation. Depending on the X-inactivation pattern of the gene, a mother and her daughters may rarely be affected. Although X-linked diseases are normally transmitted from mother to son, transmission of an X-linked mutation will occur from an affected father to each daughter, but will not occur from father to son. An IC mode of inheritance indicates no prior family history.
Indications
1. Clinical status: to confirm a clinical diagnosis in an affected patient, in an individual with unknown status (no screening/evaluation), or in unaffected relatives of an affected patient (all screening/evaluations(s) normal). The purpose of the test may be diagnostic, carrier testing, familial follow-up on a known family variant, or prenatal testing for known variant(s).
2. Treatment: to clarify the cause of an individual’s cardiovascular disease, provide information on the likelihood
of related health issues, and guide treatment.
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3. Family risk: to establish risk to other family members and future generations.
For patients with a suspected syndrome or disorder, please consider single gene sequencing or associated subpanels prior to ordering the comprehensive panel.
Testing Methods, Sensitivity, and Limitations
Next Generation Sequencing (NGS) (Analytical Detection Rate >95%)
Agilent SureSelectTM QXT technology is used with a custom capture library to target the exonic regions and intron/exon splice junctions of the relevant genes, as well as a number of UTR, intronic or promoter regions that contain previously reported mutations. Samples are pooled and sequenced on the Illumina NovaSeq platform in the Xp workflow, using 100 bp paired-end reads. The sequencing data are analyzed using a custom bioinformatics algorithm designed and validated in-house. In our validation, average coverage was greater than 200X per sample with >99.9% of regions covered at greater than 20X.
The coding exons and splice junctions of the known protein-coding RefSeq genes are assessed for the average depth of coverage (minimum of 20X) and data quality threshold values. Most exons not meeting a minimum of >20X read depth across the exon are further analyzed by Sanger sequencing. Please note that several genomic regions present difficulties in mapping or obtaining read depth >20X. These regions include, but are not limited to, UTRs, promoters, and deep intronic areas. In addition, a mutation(s) in a gene not included on the panel could be present in this patient. The following regions (hg19 coordinates) have been excluded due to lack of amenability to NGS or Sanger sequencing, high GC content, high homology, lack of known clinically significant variants, or overlap with repetitive regions: ATP7A chrX:77269723-77269729, ATP7A chrX:77278955-77279156, DMD chrX:31897426-31897627, DMD chrX:32668999-32669253, DMD chrX:32644476-32644680, DMD chrX:31627637-31627838, DMD chrX:32460213-32460334, DMD chrX:31219361-31219367, DMD chrX:31219126-31219287, DMD chrX:32644160-32644321, FKTN chr9:108368751-108368962, FLNC chr7:128498050-128498282, GATA6 chr18:19749269-19749275, GBA chr1:155207120-155207380, GBA chr1:155204774-155204902, GBA chr1:155208296-155208452, LAMP2 chrX:119604075-119604081, LEFTY2 chr1:226127049-226127311, MUT chr6:49404225-49404231, NDUFS7 chr19:1386640-1386646, PGM1 chr1:64124731-64124737, RASA2 chr3:141235158-141235284, SCN1B chr19:35521713-35521775, SDHA chr5:251441-251594, SDHA chr5:251441,251594, SDHA chr5:218459-218544, SGSH chr17:78193967- 78194168, TBX1 chr22:19748416-19748814, TRDN chr6:123851639-123851721, TRDN chr6:123576214- 123576281, TTN chr2:179518142-179518245, TTN chr2:179518336-179518439, TTN chr2:179518532- 179518635, TTN chr2:179518727-179518833, TTN chr2:179518923-179519029, TTN chr2:179519160-
179519272, TTN chr2:179519460-179519566, TTN chr2:179519627-179519733, TTN chr2:179522213- 179522319, TTN chr2:179522402-179522505, TTN chr2:179522596:179522699, TTN chr2:179522792- 179522895, TTN chr2:179522987-179523093, TTN chr2:179523183-179523289, TTN chr2:179523420- 179523532, TTN chr2:179523720-179523826, TTN chr2:179523887-179523993, TTN chr2:179526474- 179526580, TTN chr2:179526663-179526766, TTN chr2:179526857-179526960, TTN chr2:179527053- 179527156, TTN chr2:179527248-179527354, TTN chr2:179527444-179527550, TTN chr2:179527681-
179527793, TTN chr2:179527981-179528087, and TTN chr2:179528148-179528254. The exons contained within these regions will not be reflexed to Sanger sequencing if the mapping quality or coverage is poor due to high sequence homology. Any variants identified during testing in these regions are confirmed by a second method and reported.
This test will detect variants within the exons and the intron-exon boundaries of the target regions. Variants outside these regions may not be detected, including, but not limited to, UTRs, promoters, and deep intronic areas, or regions that fall into the exceptions mentioned above. This technology may not detect all small insertion/deletions and is not diagnostic for repeat expansions and structural genomic variation. In addition, a mutation(s) in a gene not included on the panel could be present in this patient.
Copy Number Variant Analysis (Analytical Detection Rate >90%)
Large duplications and deletions were called from the relative read depths on an exon-by-exon basis using a custom Exome Hidden Markov Model (XHMM) algorithm. This algorithm is designed to pick up deletions and
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duplications of two or more exons/probed regions in length. For deletions (2 exons/probed regions), the analytical
sensitivity and analytical specificity are >99%. For duplications (2 exons/probed regions), the analytical sensitivity is >80% and analytical specificity is >99%. All reported pathogenic or likely pathogenic deletions and/or duplications were confirmed by a custom aCGH platform, quantitative PCR, and/or MLPA, depending on CNV size and gene content.
Multiplex Ligation-Dependent Probe Amplification (MLPA) (Analytical Detection Rate >99%)
MLPA probe sets and reagents from MRC-Holland are used for copy number analysis of specific targets versus known control samples. False positive or negative results may occur due to rare sequence variants in target regions detected by MLPA probes. Analytical sensitivity and specificity of the MLPA method are both 99%. MLPA for Duchenne muscular dystrophy disease (DMD) will only be performed if indicated. For Duchenne muscular dystrophy, the copy numbers of all DMD exons are analyzed. Potentially pathogenic single exon deletions and duplications are confirmed by a second method. Analysis of DMD is performed in association with sequencing of the coding regions.
Exon Array (Confirmation method) (Accuracy >99%)
The customized oligonucleotide microarray (Oxford Gene Technology) is a highly-targeted exon-focused array capable of detecting medically relevant microdeletions and microduplications at a much higher resolution than traditional aCGH methods. Each array matrix has approximately one hundred and eighty thousand 60-mer oligonucleotide probes that cover the entire gene panel. This platform is designed based on human genome NCBI Build 37 (hg19) and the CGH probes are selected to target the exonic regions of 222 genes. This test does not include analysis of ALPK3, CALM2, EIF2AK4, GDF2, LZTR1, MAT2A, MEIS2, MFAP5, MIB1, PET100, PLEKHM2, PPP1CB, PRKG1, RASA2, SLMAP, and SOS2. For the majority of genes there are a minimum of 4 probes per exon. For very large exons, probes are distributed evenly along the exon with 1 probe every 125 bp. In the untargeted backbone regions, this array has one probe every 42kb. All genomic coordinates are reported using
human genome NCBI Build 37 (hg19). Copy number aberrations are identified using the Aberration Detection
Method-2 (ADM2) algorithm with a sensitivity threshold of 6.0 (Agilent Technologies). The log2 ratio threshold values to detect aberrations are < -0.25 for copy number losses and > 0.25 for copy number gains. Please note that any inconsistencies in the reported biological familial relationships could significantly change the interpretation of these results. For reported CNVs with uncertain clinical significance, continued surveillance of the medical literature for new information is recommended.
The sensitivity of this assay is estimated to be greater than 99% for microdeletions and microduplications in the exonic regions of 224 medically-relevant genes. Variant interpretation and classification is performed based on the American College of Medical Genetics standards and guidelines for the interpretation of sequence variants (Richards et al, 2015). Frequency in control populations is evaluated based on the Exome Aggregation Consortium (ExAC; http://exac.broadinstitute.org/), the Database of Genomic Variants (http://dgv.tcag.ca/dgv/app/home), and 1000 genomes (http://www.1000genomes.org/) databases. Any benign polymorphisms identified during this analysis will not be reported. Variant interpretations, based on current knowledge, may change over time as more information arises.
The following aberrations will NOT be reported and parental studies will NOT be performed:
• CNVs that are considered benign based on coverage in the Database of Genomic Variants (DGV; <http://dgv.tcag.ca/>) and/or our internal laboratory CNV database
• Gains or losses of <500 kb that do not include any known genes (<http://www.ncbi.nlm.nih.gov/refseq/>)
• Gains or losses with no known clinical significance (based on gene content and/or coverage in the DGV)
• Copy number variation of ALPK3, CALM2, EIF2AK4, GDF2, LZTR1, MAT2A, MEIS2, MFAP5, MIB1, PET100, PLEKHM2, PPP1CB, PRKG1, RASA2, SLMAP, and SOS2.
• Copy number gains and losses associated with genetic susceptibility, quantitative trait loci, pharmacogenetic alleles, and cancer predisposition
• Copy number gains and losses that are < 1.0 Mb in size and that appear to be mosaic by aCGH due to atypical
log2 ratios, unless the affected region is determined to be clinically significant based on gene content and/or coverage in the DGV
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The aCGH technology cannot detect balanced rearrangements, such as reciprocal translocations, Robertsonian translocations, inversions and balanced insertions, or imbalances that are below the resolution of this array. This technology will also not detect point mutations or small insertion/deletions below this array’s resolution that cause frameshifts, imprinting defects or other epigenetic mutations, and may not detect low level mosaicism. The failure to detect an alteration at any locus does not exclude the diagnosis of any of the disorders represented on the microarray.
The aCGH technology cannot detect balanced rearrangements, such as reciprocal translocations, Robertsonian translocations, inversions and balanced insertions, or imbalances that are below the resolution of this array. This technology will also not detect point mutations or small insertion/deletions below this array’s resolution that cause frameshifts, imprinting defects or other epigenetic mutations, and may not detect low level mosaicism. The failure to detect an alteration at any locus does not exclude the diagnosis of any of the disorders represented on the microarray.
Quantitative PCR (Confirmation method) (Accuracy >99%)
The relative quantification PCR is utilized on a Roche Universal Library Probe (UPL) system, which relates the PCR signal of the target region in one group to another. To test for genomic imbalances, both sample DNA and reference DNA is amplified with primer/probe sets that specific to the target region and a control region with known genomic copy number. Relative genomic copy numbers are calculated based on the standard ∆∆Ct formula.
Sanger Sequencing (Confirmation method) (Accuracy >99%)
Sanger sequencing, as indicated, is performed using BigDye Terminator chemistry with the ABI 3730 DNA analyzer with target specific amplicons. It also may be used to supplement specific guaranteed target regions that fail NGS sequencing due to poor quality or low depth of coverage (<20 reads) or as a confirmatory method for NGS positive results. False negative results may occur if rare variants interfere with amplification or annealing.
Variant Interpretation and Reporting
Variant interpretation and classification was performed based on the American College of Medical Genetics Standards and guidelines for the interpretation of sequence variants (PMID:25741868). Frequency in control populations were evaluated based on the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org/) , and Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org/). Potentially pathogenic variants may be confirmed by Sanger sequencing if indicated. Familial samples are only tested for certain variants by Sanger sequencing if indicated. Variants classified as likely benign in the proband were not confirmed by Sanger sequencing. We cannot rule out the possibility that variants classified as uncertain clinical significance may contribute to disease. Any benign polymorphisms identified during this analysis were not reported. Variant interpretations, based on current knowledge, may change over time as more information arises.
Turnaround Time
Results are reported to the referring physician within 10-14 business days (for prenatal samples) and 3-4 weeks (for postnatal samples) from the receipt of the specimen. Please note only targeted analysis is performed for prenatal cases, where the familial gene and mutation(s) are known.
Specimen and Shipping Requirements
Postnatal blood samples: 2 yellow-top (ACD-A or ACD-B) or 2 lavender-top (EDTA) tubes, 5-10 mL of blood from the patient are required. One blood tube from both parents is requested.
Newborn/child: 1 yellow-top (ACD-A or ACD-B) or 1 lavender-top (EDTA) tube, 2 mL of blood from the patient are required. Additionally, 1 yellow-top (ACD-A or ACD-B) or 1 lavender-top (EDTA) 5-10 mL tube of blood from
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both parents is requested.
Prenatal Specimens: 2 confluent T-25 flasks of cultured cells (originating from amniotic fluid or chorionic villi) or more than 4 mg of direct CVS tissue, or 15 mL of direct amniotic fluid (AF) as well as 1 lavender-top (EDTA) 5- 10mL tube of blood from the pregnant patient and her partner are required. Note: parental blood samples are requested for confirmation studies necessary in some cases; maternal blood is also used for maternal cell contamination studies. Please note, prenatal analysis will only be performed for known parental variants.
Extracted DNA samples: We request 20 µL DNA (50-250 ng/µL) or at minimum require 10 µL DNA (50-250 ng/µL). Causes for rejection include impurities in the test or reference DNA samples, including NaCl or KCl (>40 mM) and other salts, phenol, ethanol, heparin, EDTA (>1.5 mM), and Fe, contaminated DNA, and low concentration of DNA (<20 ng/µL).
Saliva samples: We can accept saliva specimens upon request. Saliva samples should be collected in Oragene DNA (OG-500) kits by DNA Genotek. Please contact our laboratory to obtain saliva kits.
Cheek swab: 1 cheek swab specimen collected from ORAGENE kit from the patient is required. 1 cheek swab specimen collected from ORAGENE kit from both parents is requested.
Tubes of blood, cultured cells, direct CVS, and direct AF should be kept and shipped refrigerated or at room temperature (PLEASE DO NOT FREEZE). Please note that additional samples may be required for exon array studies if ordered.
Customer Services and Genetic Counseling
Include the following with each sample: • Completed and signed test requisition form and informed consent • Billing information or payment (include copy of insurance card) • Contact information for referring physician • Testing to be performed • Indication for testing, patient’s family history, ethnic background and prior relevant test results
Send same day or overnight (check for morning delivery) to:
Sema4 1428 Madison Avenue, Atran Bldg, Room 2-25 New York, NY 10029
Contact: [email protected] Tel: 212-241-7518 Fax: 212-241-0139
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
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THE COMPREHENSIVE CARDIOMYOPATHY PANEL
Cardiomyopathies refer to diseases of the heart muscle, which can be inherited or acquired. As cardiomyopathy worsens and the heart weakens, signs and symptoms of heart failure usually occur. These signs and symptoms can include shortness of breath with physical exertion, fatigue, and swelling in the ankles, feet, legs, abdomen, and veins of the neck. Genetic testing of genes associated with inherited forms should be considered if the presence of cardiomyopathy observed in a patient cannot be explained by an acquired etiology. The Comprehensive Cardiomyopathy Panel contains the following 190 genes with six well-established subpanels: Arrythmias, Arrhythmogenic Right Ventricular Cardiomyopathy, Dilated Cardiomyopathy, Hypertrophic Cardiomyopathy, Metabolic Cardiomyopathy, and Left Ventricular Non-compaction Cardiomyopathy. Further details about these subpanels are provided on subsequent pages.
Gene MIM Disease Category OMIM Phenotype Inheritance
ABCC9
601439
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Brugada Syndrome
614050: AD Atrial fibrillation, familial, 12 608569: Cardiomyopathy, dilated, 1O 239850: AD Hypertrichotic osteochondrodysplasia
AD
ACADVL 609575 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Metabolic Cardiomyopathies
201475: AR VLCAD deficiency AR
ACTA2
102620
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies
611788: AD Aortic aneurysm, familial thoracic 6 614042: Moyamoya disease 5 613834: AD Multisystemic smooth muscle dysfunction syndrome
AD
ACTC1
102540
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction
612794: AD Atrial septal defect 5 613424: AD Cardiomyopathy, dilated, 1R
612098: AD Cardiomyopathy, hypertrophic, 11 613424: AD Left ventricular noncompaction 4
AD
ACTN2
102573
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Hypertrophic
612158: AD Cardiomyopathy, dilated, 1AA, with or without LVNC 612158: AD Cardiomyopathy, hypertrophic, 23,
AD
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Gene MIM Disease Category OMIM Phenotype Inheritance Cardiomyopathy with or without LVNC
AGK 610345 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy
614691: AR Cataract 38, AR 212350: AR Sengers syndrome
AR
AGL
610860
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Hypertrophic Cardiomyopathy; Metabolic Cardiomyopathies
232400: AR Glycogen storage disease IIIa 232400: AR Glycogen storage disease IIIb
AR
AKAP9
604001
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias; Dilated Cardiomyopathy
611820: AD ?Long QT syndrome-11
AD
ALG1 605907 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Metabolic Cardiomyopathies
608540: AR Congenital disorder of glycosylation, type Ik
AR
ALG12 607144 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Metabolic Cardiomyopathies
607143: AR Congenital disorder of glycosylation, type Ig
AR
ALMS1 606844 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease
203800: AR Alstrom syndrome AR
ALPK3 617608 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy
618052: AR Cardiomyopathy, familial hypertrophic 27
AR
ANK2
106410
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Catecholaminergic Polymorphic Ventricular Tachycardia; Long / Short Qt Syndrome; Comprehensive Arrythmias; Dilated Cardiomyopathy
600919: AD Cardiac arrhythmia, ankyrin-B-related 600919: AD Long QT syndrome 4
AD
ANKRD1
609599
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
None
None
ARSB 611542 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Metabolic Cardiomyopathies
253200: AR Mucopolysaccharidosis type VI (Maroteaux-Lamy)
AR
BAG3
603883
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
613881: AD Cardiomyopathy, dilated, 1HH 612954: AD Myopathy, myofibrillar, 6
AD
BRAF
164757
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Noonan Spectrum Disorders
211980: Adenocarcinoma of lung, somatic 115150: AD Cardiofaciocutaneous syndrome Colorectal cancer, somatic (3) 613707: AD LEOPARD syndrome 3 Melanoma, malignant, somatic (3) Nonsmall cell lung cancer, somatic (3) 613706: AD Noonan syndrome 7
AD
CACNA1C
114205
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Brugada Syndrome
611875: Brugada syndrome 3 601005: AD Timothy syndrome
AD
CACNA2D1
114204
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias; Brugada Syndrome
None
None
CACNB2
600003
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias; Brugada Syndrome
611876: Brugada syndrome 4
None
CALM1
114180
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Catecholaminergic Polymorphic Ventricular Tachycardia; Long / Short Qt Syndrome; Comprehensive Arrythmias
616247: AD Long QT syndrome 14 614916: AD Ventricular tachycardia, catecholaminergic polymorphic, 4
AD
CALM2
114182
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Catecholaminergic Polymorphic Ventricular Tachycardia; Long / Short Qt Syndrome; Comprehensive Arrythmias
616249: AD Long QT syndrome 15
AD
CALM3
114183
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Catecholaminergic Polymorphic Ventricular Tachycardia; Long / Short Qt Syndrome; Comprehensive Arrythmias
None
None
CASQ2
114251
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Catecholaminergic Polymorphic Ventricular Tachycardia; Comprehensive Arrythmias
611938: AR Ventricular tachycardia, catecholaminergic polymorphic, 2
AR
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Gene MIM Disease Category OMIM Phenotype Inheritance
CAV3
601253
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
192600: AD Cardiomyopathy, familial hypertrophic 123320: AD Creatine phosphokinase, elevated serum 611818: AD Long QT syndrome 9 614321: AD Myopathy, distal, Tateyama type 606072: AD Rippling muscle disease
AD
CAVIN4 617714 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy
None None
CBL
165360
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Noonan Spectrum Disorders
607785: AD, SM ?Juvenile myelomonocytic leukemia 613563: AD Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia
AD, SM
CBS
613381
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies
236200: AR Homocystinuria, B6-responsive and nonresponsive types 236200: AR Thrombosis, hyperhomocysteinemic
AR
CHRM2 118493 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy
None None
COL3A1 120180 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies
130050: AD Ehlers-Danlos syndrome, vascular type AD
COL5A1 120215 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies
130000: AD Ehlers-Danlos syndrome, classic type, 1 AD
COL5A2 120190 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies
130010: AD Ehlers-Danlos syndrome, classic type, 2 AD
COX10
602125
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy
256000: AR, Mitochondrial Leigh syndrome due to mitochondrial COX4 deficiency
220110: AR, Mitochondrial Mitochondrial complex IV deficiency
AR
COX15
603646
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy
615119: AR Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2 256000: AR, Mitochondrial Leigh syndrome due to cytochrome c oxidase deficiency
AR
CPT2
600650
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Hypertrophic Cardiomyopathy; Metabolic Cardiomyopathies
600649: AR CPT II deficiency, infantile 608836: AR CPT II deficiency, lethal neonatal 255110: AR, AD CPT II deficiency, myopathic, stress- induced
614212: AR, AD {Encephalopathy, acute, infection- induced, 4, susceptibility to}
AD, AR
CRYAB
123590
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy
615184: AD Cardiomyopathy, dilated, 1II 613763: AR, AD Cataract 16, multiple types 608810: AD Myopathy, myofibrillar, 2 613869: AR Myopathy, myofibrillar, fatal infantile hypertonic, alpha-B crystallin-related
AD, AR
CSRP3
600824
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
607482: ?Cardiomyopathy, dilated, 1M 612124: AD Cardiomyopathy, hypertrophic, 12
AD
CTNNA3 607667 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias
615616: AD Arrhythmogenic right ventricular dysplasia, familial, 13
AD
DES
125660
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
604765: Cardiomyopathy, dilated, 1I 601419: AR, AD Myopathy, myofibrillar, 1 181400: AD Scapuloperoneal syndrome, neurogenic, Kaeser type
AD, AR
DMD
300377
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
300376: XLR Becker muscular dystrophy 302045: XL Cardiomyopathy, dilated, 3B 310200: XLR Duchenne muscular dystrophy
XLR, XL
DOLK
610746
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Metabolic Cardiomyopathies
610768: AR Congenital disorder of glycosylation, type Im
AR
DSC2
125645
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Arrythmogenic Right Ventricular Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy
610476: AR, AD Arrhythmogenic right ventricular dysplasia 11 610476: AR, AD Arrhythmogenic right ventricular dysplasia 11 with mild palmoplantar keratoderma and woolly hair
AD, AR
DSG2 125671 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Arrythmogenic Right Ventricular
610193: AD Arrhythmogenic right ventricular dysplasia 10
AD
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
14 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
Gene MIM Disease Category OMIM Phenotype Inheritance
Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy
612877: Cardiomyopathy, dilated, 1BB
DSP
125647
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Arrythmogenic Right Ventricular Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Left Ventricular Ncompaction
607450: AD Arrhythmogenic right ventricular dysplasia 8 605676: AR Cardiomyopathy, dilated, with woolly hair and keratoderma 615821: AD Dilated cardiomyopathy with woolly hair, keratoderma, and tooth agenesis 609638: AR Epidermolysis bullosa, lethal acantholytic
612908: AD Keratosis palmoplantaris striata II 607655: AR Skin fragility-woolly hair syndrome
AD, AR
DTNA 601239 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Left Ventricular Ncompaction
604169: AD Left ventricular noncompaction 1, with or without congenital heart defects
AD
ELAC2
605367
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy
615440: AR Combined oxidative phosphorylation deficiency 17 614731: {Prostate cancer, hereditary, 2, susceptibility to}
AR
EMD
300384
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy
310300: XLR Emery-Dreifuss muscular dystrophy 1, XL
XLR, XL
EYA4 603550 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy
605362: AD ?Cardiomyopathy, dilated, 1J 601316: AD Deafness, AD 10
AD
FBN1
134797
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies
102370: AD Acromicric dysplasia 129600: AD Ectopia lentis, familial 614185: AD Geleophysic dysplasia 2 604308: MASS syndrome 616914: AD Marfan lipodystrophy syndrome 154700: AD Marfan syndrome
184900: AD Stiff skin syndrome 608328: AD Weill-Marchesani syndrome 2, dominant
AD
FBN2
612570
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies
121050: AD Contractural arachnodactyly, congenital 616118: AD Macular degeneration, early-onset
AD
FHL1
300163
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Hypertrophic Cardiomyopathy
300696: XLR Emery-Dreifuss muscular dystrophy 6, XL 300696: XLR Myopathy, XL, with postural muscle atrophy 300717: XLD Reducing body myopathy, XL 1a, severe, infantile or early childhood onset 300718: XL Reducing body myopathy, XL 1b, with late childhood or adult onset 300695: XLD Scapuloperoneal myopathy, XLD 300280: XLR ?Uruguay faciocardiomusculoskeletal syndrome
XLD, XLR, XL
FKRP
606596
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Metabolic Cardiomyopathies
613153: AR Muscular dystrophy- dystroglycanopathy (congenital with brain and eye anomalies), type A, 5 606612: AR Muscular dystrophy- dystroglycanopathy (congenital with or without mental retardation), type B, 5
607155: AR Muscular dystrophy- dystroglycanopathy (limb-girdle), type C, 5
AR
FKTN
607440
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy
611615: AR Cardiomyopathy, dilated, 1X 253800: AR Muscular dystrophy- dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 613152: AR Muscular dystrophy- dystroglycanopathy (congenital without mental retardation), type B, 4 611588: AR Muscular dystrophy- dystroglycanopathy (limb-girdle), type C, 4
AR
FLNA 300017 Comprehensive Cardiovascular; Comprehensive 314400: XLR Cardiac valvular dysplasia, XL XLD, XLR, XL
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
15 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
Gene MIM Disease Category OMIM Phenotype Inheritance
Cardiomyopathy; Aortopathies 300048: XLR Congenital short bowel syndrome 300321: XL ?FG syndrome 2 305620: XLR Frontometaphyseal dysplasia 1 300049: XLD Heterotopia, periventricular 300048: XLR Intestinal pseudoobstruction, neuronal 309350: XLD Melnick-Needles syndrome
311300: XLD Otopalatodigital syndrome, type I 304120: XLD Otopalatodigital syndrome, type II 300244: XLD Terminal osseous dysplasia
FLNC
102565
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
Cardiomyopathy, familial hypertrophic, 26 (3) 617047: AD Cardiomyopathy, familial restrictive 5 614065: AD Myopathy, distal, 4 609524: AD Myopathy, myofibrillar, 5
AD
GAA
606800
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Hypertrophic Cardiomyopathy; Metabolic Cardiomyopathies
232300: AR Glycogen storage disease II
AR
GATA4
600576
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease
607941: AD Atrial septal defect 2 614430: AD Atrioventricular septal defect 4 615542: AD ?Testicular anomalies with or without congenital heart disease 187500: AD Tetralogy of Fallot 614429: AD Ventricular septal defect 1
AD
GATA6
601656
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease
614475: AD Atrial septal defect 9 614474: AD Atrioventricular septal defect 5 600001: AD Pancreatic agenesis and congenital heart defects 217095: Persistent truncus arteriosus 187500: AD Tetralogy of Fallot
AD
GATAD1 614518 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy
614672: AR ?Cardiomyopathy, dilated, 2B AR
GBA
606463
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Metabolic Cardiomyopathies
608013: AR Gaucher disease, perinatal lethal 230800: AR Gaucher disease, type I 230900: AR Gaucher disease, type II 231000: AR Gaucher disease, type III 231005: AR Gaucher disease, type IIIC 127750: AD {Lewy body dementia, susceptibility to} 168600: IC, MF {Parkinson disease, late-onset, susceptibility to}
AD, AR, IC, MF
GBE1 607839 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Metabolic Cardiomyopathies
232500: AR Glycogen storage disease IV 263570: AR Polyglucosan body disease, adult form
AR
GJA5 121013 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias
614049: AD Atrial fibrillation, familial, 11 108770: AD Atrial standstill, digenic (GJA5/SCN5A)
AD
GLA
300644
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Hypertrophic Cardiomyopathy; Metabolic Cardiomyopathies
301500: XL Fabry disease 301500: XL Fabry disease, cardiac variant
XL
GLB1
611458
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Metabolic Cardiomyopathies
230500: AR GM1-gangliosidosis, type I 230600: AR GM1-gangliosidosis, type II 230650: AR GM1-gangliosidosis, type III 253010: AR Mucopolysaccharidosis type IVB (Morquio)
AR
GPD1L
611778
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Brugada Syndrome
611777: Brugada syndrome 2
None
GUSB 611499 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Metabolic Cardiomyopathies
253220: AR Mucopolysaccharidosis VII AR
HADHA
600890
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Metabolic Cardiomyopathies
609016: AR Fatty liver, acute, of pregnancy 609016: AR HELLP syndrome, maternal, of pregnancy 609016: AR LCHAD deficiency 609015: AR Trifunctional protein deficiency
AR
HCN4
605206
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Left Ventricular Ncompaction; Brugada Syndrome
613123: Brugada syndrome 8 163800: AD Sick sinus syndrome 2
AD
HEXB 606873 Comprehensive Cardiovascular; Comprehensive 268800: AR Sandhoff disease, infantile, juvenile, AR
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
16 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
Gene MIM Disease Category OMIM Phenotype Inheritance Cardiomyopathy; Metabolic Cardiomyopathies and adult forms
HRAS
190020
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Noonan Spectrum Disorders
109800: {Bladder cancer, somatic} 218040: AD, IC Congenital myopathy with excess of muscle spindles
218040: AD, IC Costello syndrome 162900: {Nevus sebaceous or woolly hair nevus, somatic} 163200: Schimmelpenning-Feuerstein-Mims syndrome, somatic mosaic
137550: {Spitz nevus or nevus spilus, somatic} 188470: {Thyroid carcinoma, follicular, somatic}
AD, IC
IDUA
252800
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Metabolic Cardiomyopathies
607014: AR Mucopolysaccharidosis Ih 607015: AR Mucopolysaccharidosis Ih/s 607016: AR Mucopolysaccharidosis Is
AR
ILK 602366 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy
None None
JAG1
601920
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease
118450: AD Alagille syndrome 1 617992: ?Deafness, congenital heart defects, and posterior embryotoxon 187500: AD Tetralogy of Fallot
AD
JPH2 605267 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Hypertrophic Cardiomyopathy
613873: AD Cardiomyopathy, hypertrophic, 17 AD
JUP
173325
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Arrythmogenic Right Ventricular Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy
611528: AD Arrhythmogenic right ventricular dysplasia 12 601214: AR Naxos disease
AD, AR
KCNA5
176267
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Pulmonary Hypertension
612240: AD Atrial fibrillation, familial, 7
AD
KCND3
605411
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Brugada Syndrome
616399: AD Brugada syndrome 9 607346: AD Spinocerebellar ataxia 19
AD
KCNE1
176261
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias
612347: AR Jervell and Lange-Nielsen syndrome 2 613695: AD Long QT syndrome 5
AD, AR
KCNE2
603796
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias
611493: Atrial fibrillation, familial, 4 613693: AD Long QT syndrome 6
AD
KCNE3
604433
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Brugada Syndrome
613119: Brugada syndrome 6
None
KCNE5
300328
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Brugada Syndrome
None
None
KCNH2
152427
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias; Brugada Syndrome
613688: AD Long QT syndrome 2 613688: AD {Long QT syndrome 2, acquired, susceptibility to} 609620: Short QT syndrome 1
AD
KCNJ2
600681
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Catecholaminergic Polymorphic Ventricular Tachycardia; Long / Short Qt Syndrome; Comprehensive Arrythmias
170390: AD Andersen syndrome 613980: AD Atrial fibrillation, familial, 9 609622: Short QT syndrome 3
AD
KCNJ5
600734
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias
613677: AD Hyperaldosteronism, familial, type III 613485: AD Long QT syndrome 13
AD
KCNJ8
600935
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Brugada Syndrome
None
None
KCNQ1
607542
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias
607554: AD Atrial fibrillation, familial, 3 220400: AR Jervell and Lange-Nielsen syndrome 192500: AD Long QT syndrome 1 192500: AD {Long QT syndrome 1, acquired, susceptibility to} 609621: AD Short QT syndrome 2
AD, AR
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
17 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
Gene MIM Disease Category OMIM Phenotype Inheritance
KRAS
190070
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Noonan Spectrum Disorders
108010: Arteriovenous malformation of the brain, somatic 109800: Bladder cancer, somatic 114480: Breast cancer, somatic 615278: Cardiofaciocutaneous syndrome 2 137215: Gastric cancer, somatic 601626: AD Leukemia, acute myeloid 211980: Lung cancer, somatic 609942: AD Noonan syndrome 3 260350: Pancreatic carcinoma, somatic 614470: AD RAS-associated autoimmune leukoproliferative disorder
163200: Schimmelpenning-Feuerstein-Mims syndrome, somatic mosaic
AD
LAMA4 600133 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy
615235: AD Cardiomyopathy, dilated, 1JJ AD
LAMP2
309060
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction; Metabolic Cardiomyopathies
300257: XLD Danon disease
XLD
LDB3
605906
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction
601493: AD Cardiomyopathy, dilated, 1C, with or without LVNC
601493: AD Cardiomyopathy, hypertrophic, 24 601493: AD Left ventricular noncompaction 3 609452: AD Myopathy, myofibrillar, 4
AD
LMNA
150330
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Left Ventricular Ncompaction
115200: AD Cardiomyopathy, dilated, 1A 605588: AR Charcot-Marie-Tooth disease, type 2B1 181350: AD Emery-Dreifuss muscular dystrophy 2, AD 616516: AR Emery-Dreifuss muscular dystrophy 3, AR 610140: AD Heart-hand syndrome, Slovenian type 176670: AR, AD Hutchinson-Gilford progeria 151660: AD Lipodystrophy, familial partial, type 2 212112: AD Malouf syndrome 248370: AR Mandibuloacral dysplasia 613205: AD Muscular dystrophy, congenital 275210: AR Restrictive dermopathy, lethal
AD, AR
MAP2K1
176872
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Noonan Spectrum Disorders
615279: Cardiofaciocutaneous syndrome 3
None
MAP2K2
601263
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Noonan Spectrum Disorders
615280: Cardiofaciocutaneous syndrome 4
None
MED12
300188
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies
309520: XLR Lujan-Fryns syndrome 300895: XLR Ohdo syndrome, XL 305450: XLR Opitz-Kaveggia syndrome
XLR, XL
MIB1 608677 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Left Ventricular Ncompaction
615092: AD Left ventricular noncompaction 7 AD
MLYCD 606761 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy
248360: AR Malonyl-CoA decarboxylase deficiency AR
MTO1 614667 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Metabolic Cardiomyopathies
614702: AR Combined oxidative phosphorylation deficiency 10
AR
MUT 609058 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy
251000: AR Methylmalonic aciduria, mut(0) type AR
MYBPC3
600958
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction
615396: AD Cardiomyopathy, dilated, 1MM 115197: AD Cardiomyopathy, hypertrophic, 4 615396: AD Left ventricular noncompaction 10
AD
MYH11 160745 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies
132900: AD Aortic aneurysm, familial thoracic 4 AD
MYH6
160710
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
614089: Atrial septal defect 3 613252: Cardiomyopathy, dilated, 1EE 613251: AD Cardiomyopathy, hypertrophic, 14
AD
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
18 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
Gene MIM Disease Category OMIM Phenotype Inheritance 614090: {Sick sinus syndrome 3}
MYH7
160760
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction
613426: AD Cardiomyopathy, dilated, 1S 192600: AD Cardiomyopathy, hypertrophic, 1 160500: AD Laing distal myopathy 613426: AD Left ventricular noncompaction 5 608358: AD Myopathy, myosin storage, AD 255160: AR Myopathy, myosin storage, AR
181430: AD Scapuloperoneal syndrome, myopathic type
AD, AR
MYL2 160781 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Hypertrophic Cardiomyopathy
608758: AD Cardiomyopathy, hypertrophic, 10 AD
MYL3 160790 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Hypertrophic Cardiomyopathy
608751: AR, AD Cardiomyopathy, hypertrophic, 8 AD, AR
MYLK 600922 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies
613780: AD Aortic aneurysm, familial thoracic 7 AD
MYLK2 606566 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Hypertrophic Cardiomyopathy
192600: AD Cardiomyopathy, hypertrophic, 1, digenic
AD
MYOM1 603508 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Hypertrophic Cardiomyopathy
None None
MYOZ2 605602 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Hypertrophic Cardiomyopathy
613838: AD Cardiomyopathy, hypertrophic, 16 AD
MYPN
608517
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
615248: AD Cardiomyopathy, dilated, 1KK 615248: AD Cardiomyopathy, familial restrictive, 4
615248: AD Cardiomyopathy, hypertrophic, 22 617336: AR Nemaline myopathy 11, AR
AD, AR
NDUFA10 603835 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy
256000: AR, Mitochondrial Leigh syndrome AR
NDUFA12 614530 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy
256000: AR, Mitochondrial Leigh syndrome due to mitochondrial complex 1 deficiency
AR
NDUFA2 602137 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy
256000: AR, Mitochondrial Leigh syndrome due to mitochondrial complex I deficiency
AR
NDUFA9 603834 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy
256000: AR, Mitochondrial Leigh syndrome due to mitochondrial complex I deficiency
AR
NDUFAF2 609653 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy
252010: AR, XLD, Mitochondrial Mitochondrial complex I deficiency
AR, XLD
NDUFAF6 612392 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy
256000: AR, Mitochondrial Leigh syndrome due to mitochondrial complex I deficiency
AR
NDUFS3
603846
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy
256000: AR, Mitochondrial Leigh syndrome due to mitochondrial complex I deficiency
252010: AR, XLD, Mitochondrial Mitochondrial complex I deficiency
AR, XLD
NDUFS4
602694
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy
256000: AR, Mitochondrial Leigh syndrome 252010: AR, XLD, Mitochondrial Mitochondrial complex I deficiency
AR, XLD
NDUFS7 601825 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy
256000: AR, Mitochondrial Leigh syndrome AR
NDUFS8 602141 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy
256000: AR, Mitochondrial Leigh syndrome due to mitochondrial complex I deficiency
AR
NEBL 605491 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy
None None
NEXN
613121
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
613122: AD Cardiomyopathy, dilated, 1CC 613876: AD Cardiomyopathy, hypertrophic, 20
AD
NKX2-5
600584
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Congenital Heart Disease
108900: AD Atrial septal defect 7, with or without AV conduction defects 217095: Conotruncal heart malformations, variable 614435: AD Hypoplastic left heart syndrome 2 225250: AD Hypothyroidism, congenital nongoitrous, 5 187500: AD Tetralogy of Fallot 614432: AD Ventricular septal defect 3
AD
NOTCH1
190198
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies; Congenital Heart Disease
616028: AD Adams-Oliver syndrome 5 109730: AD Aortic valve disease 1
AD
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
19 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
Gene MIM Disease Category OMIM Phenotype Inheritance
NPPA 108780 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias
612201: AD Atrial fibrillation, familial, 6 615745: AR Atrial standstill 2
AD, AR
NRAS
164790
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Noonan Spectrum Disorders
114500: Colorectal cancer, somatic 162900: Epidermal nevus, somatic 137550: Melanocytic nevus syndrome, congenital, somatic 249400: Neurocutaneous melanosis, somatic 613224: AD Noonan syndrome 6 614470: ?RAS-associated autoimmune lymphoproliferative syndrome type IV, somatic 163200: Schimmelpenning-Feuerstein-Mims syndrome, somatic mosaic 188470: Thyroid carcinoma, follicular, somatic
AD
OBSCN Comprehensive Cardiovascular; Comprehensive
Cardiomyopathy; Dilated Cardiomyopathy
PCCA 232000 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Metabolic Cardiomyopathies
606054: AR Propionicacidemia AR
PCCB 232050 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Metabolic Cardiomyopathies
606054: AR Propionicacidemia AR
PDLIM3 605889 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Hypertrophic Cardiomyopathy
None None
PET100 614770 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy
220110: AR, Mitochondrial Mitochondrial complex IV deficiency
AR
PGM1 171900 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy
614921: AR Congenital disorder of glycosylation, type It
AR
PHYH 602026 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy
266500: AR Refsum disease AR
PKP2
602861
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Arrythmogenic Right Ventricular Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Brugada Syndrome
609040: AD Arrhythmogenic right ventricular dysplasia 9
AD
PLEKHM2 609613 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Left Ventricular Ncompaction
None None
PLN
172405
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction
609909: Cardiomyopathy, dilated, 1P 613874: AD Cardiomyopathy, hypertrophic, 18
AD
PLOD1 153454 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies
225400: AR Ehlers-Danlos syndrome, kyphoscoliotic type, 1
AR
PMM2 601785 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy
212065: AR Congenital disorder of glycosylation, type Ia
AR
PRDM16
605557
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Left Ventricular Ncompaction
615373: AD Cardiomyopathy, dilated, 1LL 615373: AD Left ventricular noncompaction 8
AD
PRKAG2
602743
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Hypertrophic Cardiomyopathy
600858: AD Cardiomyopathy, hypertrophic 6 261740: AD Glycogen storage disease of heart, lethal congenital 194200: ?AD Wolff-Parkinson-White syndrome
AD
PRKG1 176894 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies
615436: AD Aortic aneurysm, familial thoracic 8 AD
PTPN11
176876
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Hypertrophic Cardiomyopathy; Noonan Spectrum Disorders
151100: AD LEOPARD syndrome 1 607785: Leukemia, juvenile myelomonocytic, somatic 156250: AD Metachondromatosis 163950: AD Noonan syndrome 1
AD
RAF1
164760
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Noonan Spectrum Disorders
615916: AD Cardiomyopathy, dilated, 1NN 611554: LEOPARD syndrome 2 611553: AD Noonan syndrome 5
AD
RANGRF
607954
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Brugada Syndrome
None
None
RASA1 139150 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Hereditary Hemorrhagic
605462: Basal cell carcinoma, somatic 608354: AD Capillary malformation-arteriovenous
AD
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
20 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
Gene MIM Disease Category OMIM Phenotype Inheritance
Telangiectasia malformation 608355: AD Parkes Weber syndrome
RBM20 613171 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy
613172: AD Cardiomyopathy, dilated, 1DD AD
RIT1
609591
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Noonan Spectrum Disorders
615355: AD Noonan syndrome 8
AD
RYR2
180902
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Catecholaminergic Polymorphic Ventricular Tachycardia; Arrythmogenic Right Ventricular Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Left Ventricular Ncompaction
600996: AD Arrhythmogenic right ventricular dysplasia 2 604772: AD Ventricular tachycardia, catecholaminergic polymorphic, 1
AD
SCN10A
604427
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Brugada Syndrome
615551: AD Episodic pain syndrome, familial, 2
AD
SCN1B
600235
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Brugada Syndrome
615377: AD Atrial fibrillation, familial, 13 612838: Brugada syndrome 5 612838: Cardiac conduction defect, nonspecific 604233: AD Epilepsy, generalized, with febrile seizures plus, type 1 617350: AR Epileptic encephalopathy, early infantile, 52
AD, AR
SCN2B
601327
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Brugada Syndrome
615378: AD Atrial fibrillation, familial, 14
AD
SCN3B
608214
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Brugada Syndrome
613120: AD Atrial fibrillation, familial, 16 613120: AD Brugada syndrome 7
AD
SCN4B
608256
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias
611819: AD Atrial fibrillation, familial, 17 611819: AD Long QT syndrome-10
AD
SCN5A
600163
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias; Dilated Cardiomyopathy; Left Ventricular Ncompaction; Brugada Syndrome
614022: AD Atrial fibrillation, familial, 10 601144: AD Brugada syndrome 1 601154: AD Cardiomyopathy, dilated, 1E 113900: AD Heart block, nonprogressive 113900: AD Heart block, progressive, type IA 603830: AD Long QT syndrome-3
608567: AR Sick sinus syndrome 1 272120: AR {Sudden infant death syndrome, susceptibility to} 603829: Ventricular fibrillation, familial, 1
AD, AR
SCO1 603644 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy
220110: AR, Mitochondrial Mitochondrial complex IV deficiency
AR
SDHA
600857
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy
613642: Cardiomyopathy, dilated, 1GG 256000: AR, Mitochondrial Leigh syndrome 252011: AR Mitochondrial respiratory chain complex II deficiency 614165: AD Paragangliomas 5
AD, AR
SDHAF1 612848 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy
252011: AR Mitochondrial complex II deficiency AR
SGCD 601411 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy
606685: Cardiomyopathy, dilated, 1L 601287: AR Muscular dystrophy, limb-girdle, AR 6
AR
SGSH 605270 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy
252900: AR Mucopolysaccharidosis type IIIA (Sanfilippo A)
AR
SHOC2
602775
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Noonan Spectrum Disorders
607721: AD Noonan-like syndrome with loose anagen hair
AD
SKI 164780 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies
182212: AD Shprintzen-Goldberg syndrome AD
SLC22A5
603377
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Metabolic Cardiomyopathies
212140: AR Carnitine deficiency, systemic primary
AR
SLC25A20 613698 Comprehensive Cardiovascular; Comprehensive 212138: AR Carnitine-acylcarnitine translocase AR
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
21 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
Gene MIM Disease Category OMIM Phenotype Inheritance Cardiomyopathy; Metabolic Cardiomyopathies deficiency
SLC2A10 606145 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies
208050: AR Arterial tortuosity syndrome AR
SLMAP
602701
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Brugada Syndrome
None
None
SMAD3 603109 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies
613795: AD Loeys-Dietz syndrome 3 AD
SMAD4
600993
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies; Hereditary Hemorrhagic Telangiectasia
175050: AD Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome 139210: AD Myhre syndrome
260350: Pancreatic cancer, somatic 174900: AD Polyposis, juvenile intestinal
AD
SNTA1
601017
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias
612955: AD Long QT syndrome 12
AD
SOS1
182530
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Noonan Spectrum Disorders
135300: AD ?Fibromatosis, gingival, 1 610733: AD Noonan syndrome 4
AD
SURF1
185620
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy
616684: AR Charcot-Marie-Tooth disease, type 4K 256000: AR, Mitochondrial Leigh syndrome, due to COX IV deficiency
AR
TAZ
300394
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Left Ventricular Ncompaction; Metabolic Cardiomyopathies
302060: XLR Barth syndrome
XLR
TBX1
602054
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease
217095: Conotruncal anomaly face syndrome 188400: AD DiGeorge syndrome
187500: AD Tetralogy of Fallot 192430: AD Velocardiofacial syndrome
AD
TBX5 601620 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease
142900: AD Holt-Oram syndrome AD
TCAP
604488
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
607487: AD Cardiomyopathy, hypertrophic, 25 601954: AR Muscular dystrophy, limb-girdle, AR 7
AD, AR
TGFB2 190220 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies
614816: AD Loeys-Dietz syndrome 4 AD
TGFB3
190230
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Arrythmogenic Right Ventricular Cardiomyopathy; Aortopathies; Comprehensive Arrythmias
107970: AD Arrhythmogenic right ventricular dysplasia 1 615582: AD Loeys-Dietz syndrome 5
AD
TGFBR1
190181
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies
609192: AD Loeys-Dietz syndrome 1 132800: AD {Multiple self-healing squamous epithelioma, susceptibility to}
AD
TGFBR2
190182
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies
614331: Colorectal cancer, hereditary nonpolyposis, type 6
133239: Esophageal cancer, somatic 610168: AD Loeys-Dietz syndrome 2
AD
TMEM43
612048
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Arrythmogenic Right Ventricular Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy
604400: AD Arrhythmogenic right ventricular dysplasia 5 614302: AD Emery-Dreifuss muscular dystrophy 7, AD
AD
TMEM70 612418 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy
614052: AR Mitochondrial complex V (ATP synthase) deficiency, nuclear type 2
AR
TMPO 188380 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy
None None
TNNC1
191040
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
611879: Cardiomyopathy, dilated, 1Z 613243: AD Cardiomyopathy, hypertrophic, 13
AD
TNNI3
191044
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction
613286: Cardiomyopathy, dilated, 1FF 611880: AR ?Cardiomyopathy, dilated, 2A 115210: AD Cardiomyopathy, familial restrictive, 1 613690: AD Cardiomyopathy, hypertrophic, 7
AD, AR
TNNT2 191045 Comprehensive Cardiovascular; Comprehensive 601494: AD Cardiomyopathy, dilated, 1D AD
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
22 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
Gene MIM Disease Category OMIM Phenotype Inheritance
Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction
612422: AD Cardiomyopathy, familial restrictive, 3 115195: AD Cardiomyopathy, hypertrophic, 2 601494: AD Left ventricular noncompaction 6
TPM1
191010
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction
611878: AD Cardiomyopathy, dilated, 1Y 115196: AD Cardiomyopathy, hypertrophic, 3
611878: AD Left ventricular noncompaction 9
AD
TRDN
603283
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Catecholaminergic Polymorphic Ventricular Tachycardia; Long / Short Qt Syndrome; Comprehensive Arrythmias
615441: AR Ventricular tachycardia, catecholaminergic polymorphic, 5, with or without muscle weakness
AR
TRPM4
606936
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Brugada Syndrome
604559: AD Progressive familial heart block, type IB
AD
TTN
188840
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy
604145: Cardiomyopathy, dilated, 1G 613765: AD Cardiomyopathy, familial hypertrophic, 9 608807: AR Muscular dystrophy, limb-girdle, AR 10 603689: Myopathy, proximal, with early respiratory muscle involvement
611705: AR Salih myopathy 600334: AD Tibial muscular dystrophy, tardive
AD, AR
TTR
176300
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
105210: AD Amyloidosis, hereditary, transthyretin- related 115430: AD Carpal tunnel syndrome, familial 145680: AD [Dystransthyretinemic hyperthyroxinemia]
AD
TXNRD2 606448 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy
617825: AR ?Glucocorticoid deficiency 5 AR
VCL
193065
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction
611407: Cardiomyopathy, dilated, 1W 613255: AD Cardiomyopathy, hypertrophic, 15
AD
1. Abbreviations: Autosomal Dominant (AD); Autosomal Recession (AR); Isolated Cases (IC); Multifactorial (MF); Somatic Mutations (SM; Note: somatic mutations are not reported); XL (X-linked); XLD (X-linked Dominant); and XLR (X-linked Recessive).
2. DMD: The following DMD hg19 coordinates have been excluded from this assay: chrX:31897426-31897627, chrX:32668999-32669253,
chrX:32644476-32644680, chrX:31627637-31627838, chrX:32460213-32460334, chrX:31219361-31219367, chrX:31219126-31219287,
chrX:32644160-32644321
3. FKTN: The following FKTN hg19 coordinates have been excluded from this assay: chr9:108368751-108368962
4. FLNC: The following FLNC hg19 coordinates have been excluded from this assay: chr7:128498050-128498282
5. GATA6: The following GATA6 hg19 coordinates have been excluded from this assay: chr18:19749269-19749275
6. GBA: The following GBA hg19 coordinates have been excluded from this assay: chr1:155207120-155207380, chr1:155204774-
155204902, chr1:155208296-155208452
7. LAMP2: The following LAMP2 hg19 coordinates have been excluded from this assay: chrX:119604075-119604081
8. MUT: The following MUT hg19 coordinates have been excluded from this assay: chr6:49404225-49404231
9. NDUFS7: The following NDUFS7 hg19 coordinates have been excluded from this assay: chr19:1386640-1386646
10. PGM1: The following PGM1 hg19 coordinates have been excluded from this assay: chr1:64124731-64124737
11. SCN1B: The following SCN1B hg19 coordinates have been excluded from this assay: chr19:35521713-35521775
12. SDHA: The following SDHA hg19 coordinates have been excluded from this assay: chr5:251441-251594, chr5:254496-254632,
chr5:218459-218544
13. SGSH: The following SGSH hg19 coordinates have been excluded from this assay: chr17:78193967-78194168
14. TBX1: The following TBX1 hg19 coordinates have been excluded from this assay: chr22:19748416-19748814
15. TRDN: The following TRDN hg19 coordinates have been excluded from this assay: chr6:123851639-123851721, chr6:123576214- 123576281
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
23 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
DILATED CARDIOMYOPATHY (DCM) SUBPANEL
Dilated cardiomyopathy (DCM) is characterized by the presence of left ventricular dilation and left ventricular systolic dysfunction in the absence of abnormal loading conditions or coronary artery disease. DCM usually presents with heart failure with symptoms of congestion, reduced cardiac output, arrhythmias, and/or thromboembolic disease. Right ventricular dilation may be present but is not necessary for the diagnosis. The most prevalent cause of DCMs is ischemic injury due to prior myocardial infarction from coronary artery disease.
The Dilated Cardiomyopathy (DCM) Subpanel contains the following 57 genes.
Gene MIM Disease Category OMIM Phenotype Inheritance
ABCC9
601439
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Brugada Syndrome
614050: AD Atrial fibrillation, familial, 12 608569: Cardiomyopathy, dilated, 1O 239850: AD Hypertrichotic osteochondrodysplasia
AD
ACTC1
102540
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction
612794: AD Atrial septal defect 5 613424: AD Cardiomyopathy, dilated, 1R 612098: AD Cardiomyopathy, hypertrophic, 11
613424: AD Left ventricular noncompaction 4
AD
ACTN2
102573
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
612158: AD Cardiomyopathy, dilated, 1AA, with or without LVNC 612158: AD Cardiomyopathy, hypertrophic, 23, with or without LVNC
AD
AKAP9
604001
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias; Dilated Cardiomyopathy
611820: AD ?Long QT syndrome-11
AD
ANK2
106410
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Catecholaminergic Polymorphic Ventricular Tachycardia; Long / Short Qt Syndrome; Comprehensive Arrythmias; Dilated Cardiomyopathy
600919: AD Cardiac arrhythmia, ankyrin-B- related 600919: AD Long QT syndrome 4
AD
ANKRD1
609599 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
None
None
BAG3
603883
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
613881: AD Cardiomyopathy, dilated, 1HH 612954: AD Myopathy, myofibrillar, 6
AD
CACNA1C
114205
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Brugada Syndrome
611875: Brugada syndrome 3 601005: AD Timothy syndrome
AD
CAV3
601253
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
192600: AD Cardiomyopathy, familial hypertrophic 123320: AD Creatine phosphokinase, elevated serum 611818: AD Long QT syndrome 9
614321: AD Myopathy, distal, Tateyama type 606072: AD Rippling muscle disease
AD
CAVIN4
617714
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy
None
None
CRYAB
123590
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy
615184: AD Cardiomyopathy, dilated, 1II 613763: AR, AD Cataract 16, multiple types 608810: AD Myopathy, myofibrillar, 2 613869: AR Myopathy, myofibrillar, fatal infantile hypertonic, alpha-B crystallin-related
AD, AR
CSRP3
600824
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
607482: ?Cardiomyopathy, dilated, 1M 612124: AD Cardiomyopathy, hypertrophic, 12
AD
DES
125660 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Dilated
604765: Cardiomyopathy, dilated, 1I 601419: AR, AD Myopathy, myofibrillar, 1 181400: AD Scapuloperoneal syndrome,
AD, AR
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
24 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
Gene MIM Disease Category OMIM Phenotype Inheritance Cardiomyopathy; Hypertrophic Cardiomyopathy neurogenic, Kaeser type
DMD
300377 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
300376: XLR Becker muscular dystrophy 302045: XL Cardiomyopathy, dilated, 3B 310200: XLR Duchenne muscular dystrophy
XLR, XL
DOLK
610746
Comprehensive Cardiovascular;
Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Metabolic Cardiomyopathy
610768: AR Congenital disorder of glycosylation, type Im
AR
DSC2
125645
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Arrythmogenic Right Ventricular Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy
610476: AR, AD Arrhythmogenic right ventricular dysplasia 11 610476: AR, AD Arrhythmogenic right ventricular dysplasia 11 with mild palmoplantar keratoderma and woolly hair
AD, AR
DSG2
125671
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Arrythmogenic Right Ventricular Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy
610193: AD Arrhythmogenic right ventricular dysplasia 10 612877: Cardiomyopathy, dilated, 1BB
AD
DSP
125647
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Arrythmogenic Right Ventricular Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Left Ventricular Ncompaction
607450: AD Arrhythmogenic right ventricular dysplasia 8 605676: AR Cardiomyopathy, dilated, with woolly hair and keratoderma 615821: AD Dilated cardiomyopathy with woolly hair, keratoderma, and tooth agenesis 609638: AR Epidermolysis bullosa, lethal acantholytic 612908: AD Keratosis palmoplantaris striata II 607655: AR Skin fragility-woolly hair syndrome
AD, AR
ELAC2
605367
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy
615440: AR Combined oxidative phosphorylation deficiency 17
614731: {Prostate cancer, hereditary, 2, susceptibility to}
AR
EMD
300384
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy
310300: XLR Emery-Dreifuss muscular dystrophy 1, XL
XLR, XL
EYA4
603550 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy
605362: AD ?Cardiomyopathy, dilated, 1J 601316: AD Deafness, AD 10
AD
FKTN
607440
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy
611615: AR Cardiomyopathy, dilated, 1X 253800: AR Muscular dystrophy- dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 613152: AR Muscular dystrophy- dystroglycanopathy (congenital without mental retardation), type B, 4 611588: AR Muscular dystrophy- dystroglycanopathy (limb-girdle), type C, 4
AR
FLNC
102565
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
Cardiomyopathy, familial hypertrophic, 26 (3) 617047: AD Cardiomyopathy, familial restrictive 5 614065: AD Myopathy, distal, 4 609524: AD Myopathy, myofibrillar, 5
AD
GATAD1
614518
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy
614672: AR ?Cardiomyopathy, dilated, 2B
AR
ILK
602366 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy
None
None
JUP
173325
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Arrythmogenic Right Ventricular Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy
611528: AD Arrhythmogenic right ventricular dysplasia 12 601214: AR Naxos disease
AD, AR
LAMA4
600133
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy
615235: AD Cardiomyopathy, dilated, 1JJ
AD
LAMP2 309060 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated
300257: XLD Danon disease XLD
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
25 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
Gene MIM Disease Category OMIM Phenotype Inheritance
Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction; Metabolic Cardiomyopathy
LDB3
605906
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction
601493: AD Cardiomyopathy, dilated, 1C, with or without LVNC 601493: AD Cardiomyopathy, hypertrophic, 24 601493: AD Left ventricular noncompaction 3 609452: AD Myopathy, myofibrillar, 4
AD
LMNA
150330
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Left Ventricular Ncompaction
115200: AD Cardiomyopathy, dilated, 1A 605588: AR Charcot-Marie-Tooth disease, type 2B1 181350: AD Emery-Dreifuss muscular dystrophy 2, AD 616516: AR Emery-Dreifuss muscular dystrophy 3, AR 610140: AD Heart-hand syndrome, Slovenian type 176670: AR, AD Hutchinson-Gilford progeria 151660: AD Lipodystrophy, familial partial, type 2 212112: AD Malouf syndrome 248370: AR Mandibuloacral dysplasia 613205: AD Muscular dystrophy, congenital 275210: AR Restrictive dermopathy, lethal
AD, AR
MYBPC3
600958
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction
615396: AD Cardiomyopathy, dilated, 1MM 115197: AD Cardiomyopathy, hypertrophic, 4
615396: AD Left ventricular noncompaction 10
AD
MYH6
160710
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
614089: Atrial septal defect 3 613252: Cardiomyopathy, dilated, 1EE 613251: AD Cardiomyopathy, hypertrophic, 14 614090: {Sick sinus syndrome 3}
AD
MYH7
160760
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction
613426: AD Cardiomyopathy, dilated, 1S 192600: AD Cardiomyopathy, hypertrophic, 1 160500: AD Laing distal myopathy 613426: AD Left ventricular noncompaction 5 608358: AD Myopathy, myosin storage, AD 255160: AR Myopathy, myosin storage, AR 181430: AD Scapuloperoneal syndrome, myopathic type
AD, AR
MYPN
608517
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
615248: AD Cardiomyopathy, dilated, 1KK 615248: AD Cardiomyopathy, familial restrictive, 4 615248: AD Cardiomyopathy, hypertrophic, 22 617336: AR Nemaline myopathy 11, AR
AD, AR
NEBL
605491 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy
None
None
NEXN
613121
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
613122: AD Cardiomyopathy, dilated, 1CC 613876: AD Cardiomyopathy, hypertrophic, 20
AD
OBSCN Comprehensive Cardiovascular;
Comprehensive Cardiomyopathy; Dilated Cardiomyopathy
PKP2
602861
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Arrythmogenic Right Ventricular Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Brugada Syndrome
609040: AD Arrhythmogenic right ventricular dysplasia 9
AD
PLN
172405
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction
609909: Cardiomyopathy, dilated, 1P 613874: AD Cardiomyopathy, hypertrophic, 18
AD
PRDM16
605557 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Left Ventricular Ncompaction
615373: AD Cardiomyopathy, dilated, 1LL 615373: AD Left ventricular noncompaction 8
AD
RAF1 164760 Comprehensive Cardiovascular; 615916: AD Cardiomyopathy, dilated, 1NN AD
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
26 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
Gene MIM Disease Category OMIM Phenotype Inheritance
Comprehensive Cardiomyopathy; Congenital Heart Disease; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Noonan Spectrum Disorders
611554: LEOPARD syndrome 2 611553: AD Noonan syndrome 5
RBM20
613171
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy
613172: AD Cardiomyopathy, dilated, 1DD
AD
RYR2
180902
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Catecholaminergic Polymorphic Ventricular Tachycardia; Arrythmogenic Right Ventricular Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Left Ventricular Ncompaction
600996: AD Arrhythmogenic right ventricular dysplasia 2
604772: AD Ventricular tachycardia, catecholaminergic polymorphic, 1
AD
SCN5A
600163
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias; Dilated Cardiomyopathy; Left Ventricular Ncompaction; Brugada Syndrome
614022: AD Atrial fibrillation, familial, 10 601144: AD Brugada syndrome 1 601154: AD Cardiomyopathy, dilated, 1E 113900: AD Heart block, nonprogressive 113900: AD Heart block, progressive, type IA 603830: AD Long QT syndrome-3 608567: AR Sick sinus syndrome 1
272120: AR {Sudden infant death syndrome, susceptibility to} 603829: Ventricular fibrillation, familial, 1
AD, AR
SGCD
601411
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy
606685: Cardiomyopathy, dilated, 1L 601287: AR Muscular dystrophy, limb-girdle, AR 6
AR
SLC22A5
603377 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Metabolic Cardiomyopathy
212140: AR Carnitine deficiency, systemic primary
AR
TAZ
300394
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Left Ventricular Ncompaction; Metabolic Cardiomyopathy
302060: XLR Barth syndrome
XLR
TCAP
604488 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
607487: AD Cardiomyopathy, hypertrophic, 25 601954: AR Muscular dystrophy, limb-girdle, AR 7
AD, AR
TMEM43
612048
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Arrythmogenic Right Ventricular Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy
604400: AD Arrhythmogenic right ventricular dysplasia 5 614302: AD Emery-Dreifuss muscular dystrophy 7, AD
AD
TNNC1
191040 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
611879: Cardiomyopathy, dilated, 1Z 613243: AD Cardiomyopathy, hypertrophic, 13
AD
TNNI3
191044
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction
613286: Cardiomyopathy, dilated, 1FF 611880: AR ?Cardiomyopathy, dilated, 2A 115210: AD Cardiomyopathy, familial restrictive, 1 613690: AD Cardiomyopathy, hypertrophic, 7
AD, AR
TNNT2
191045
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction
601494: AD Cardiomyopathy, dilated, 1D 612422: AD Cardiomyopathy, familial restrictive, 3 115195: AD Cardiomyopathy, hypertrophic, 2 601494: AD Left ventricular noncompaction 6
AD
TPM1
191010
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction
611878: AD Cardiomyopathy, dilated, 1Y 115196: AD Cardiomyopathy, hypertrophic, 3 611878: AD Left ventricular noncompaction 9
AD
TTN
188840
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy
604145: Cardiomyopathy, dilated, 1G 613765: AD Cardiomyopathy, familial hypertrophic, 9
608807: AR Muscular dystrophy, limb-girdle, AR 10 603689: Myopathy, proximal, with early respiratory muscle involvement 611705: AR Salih myopathy 600334: AD Tibial muscular dystrophy, tardive
AD, AR
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
27 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
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Gene MIM Disease Category OMIM Phenotype Inheritance
TTR
176300
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
105210: AD Amyloidosis, hereditary, transthyretin-related 115430: AD Carpal tunnel syndrome, familial 145680: AD [Dystransthyretinemic hyperthyroxinemia]
AD
TXNRD2
606448 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy
617825: AR ?Glucocorticoid deficiency 5
AR
VCL
193065
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction
611407: Cardiomyopathy, dilated, 1W 613255: AD Cardiomyopathy, hypertrophic, 15
AD
1. Abbreviations: Autosomal Dominant (AD); Autosomal Recession (AR); Isolated Cases (IC); Multifactorial (MF); Somatic Mutations (SM; Note: somatic mutations are not reported); XL (X-linked); XLD (X-linked Dominant); and XLR (X-linked Recessive).
2. DMD: The following DMD hg19 coordinates have been excluded from this assay: chrX:31897426-31897627, chrX:32668999-32669253,
chrX:32644476-32644680, chrX:31627637-31627838, chrX:32460213-32460334, chrX:31219361-31219367, chrX:31219126-31219287,
chrX:32644160-32644321
3. FKTN: The following FKTN hg19 coordinates have been excluded from this assay: chr9:108368751-108368962
4. FLNC: The following FLNC hg19 coordinates have been excluded from this assay: chr7:128498050-128498282
5. LAMP2: The following LAMP2 hg19 coordinates have been excluded from this assay: chrX:119604075-119604081
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
28 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY (ARVC) SUBPANEL
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by right ventricular dysfunction, ventricular arrhythmias, and progressive fibrofatty replacement of the myocardium resulting in an increased risk of sudden death in young individuals and athletes. In particular, the arrhythmias in ARVC, which arise from the right ventricle, have left bundle branch block morphology, which can be seen with an electrocardiogram. Cardiac MRI studies have also identified regional left ventricular dysfunction among individuals with ARVC. Overall, ARVC is marked by age-dependent penetrance with most patients presenting in the second to fourth decade of life. Of note, males were more likely to have arrhythmia events in analyses of individuals with genetically confirmed ARVC. Since many forms of cardiomyopathy can mimic aspects of ARVC, clinical and genetic testing is recommended for proper management.
The Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) Subpanel contains the following 8 genes.
Gene MIM Disease Category OMIM Phenotype Inheritance
DSC2
125645
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Arrythmogenic Right Ventricular Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy
610476: AR, AD Arrhythmogenic right ventricular dysplasia 11 610476: AR, AD Arrhythmogenic right ventricular dysplasia 11 with mild palmoplantar keratoderma and woolly hair
AD, AR
DSG2
125671
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Arrythmogenic Right Ventricular Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy
610193: AD Arrhythmogenic right ventricular dysplasia 10 612877: Cardiomyopathy, dilated, 1BB
AD
DSP
125647
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Arrythmogenic Right Ventricular Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Left Ventricular Ncompaction
607450: AD Arrhythmogenic right ventricular dysplasia 8 605676: AR Cardiomyopathy, dilated, with woolly hair and keratoderma 615821: AD Dilated cardiomyopathy with woolly hair, keratoderma, and tooth agenesis 609638: AR Epidermolysis bullosa, lethal acantholytic 612908: AD Keratosis palmoplantaris striata II 607655: AR Skin fragility-woolly hair syndrome
AD, AR
JUP
173325
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Arrythmogenic Right Ventricular Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy
611528: AD Arrhythmogenic right ventricular dysplasia 12 601214: AR Naxos disease
AD, AR
PKP2
602861
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Arrythmogenic Right Ventricular Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Brugada Syndrome
609040: AD Arrhythmogenic right ventricular dysplasia 9
AD
RYR2
180902
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Catecholaminergic Polymorphic Ventricular Tachycardia; Arrythmogenic Right Ventricular Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Left Ventricular Ncompaction
600996: AD Arrhythmogenic right ventricular dysplasia 2 604772: AD Ventricular tachycardia, catecholaminergic polymorphic, 1
AD
TGFB3
190230
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Arrythmogenic Right Ventricular Cardiomyopathy; Aortopathies; Comprehensive Arrythmias
107970: AD Arrhythmogenic right ventricular dysplasia 1 615582: AD Loeys-Dietz syndrome 5
AD
TMEM43
612048
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Arrythmogenic Right Ventricular Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy
604400: AD Arrhythmogenic right ventricular dysplasia 5 614302: AD Emery-Dreifuss muscular dystrophy 7, AD
AD
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
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1. Abbreviations: Autosomal Dominant (AD); Autosomal Recession (AR); Isolated Cases (IC); Multifactorial (MF); Somatic Mutations (SM; Note: somatic mutations are not reported); XL (X-linked); XLD (X-linked Dominant); and XLR (X-linked Recessive).
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
30 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
HYPERTROPHIC CARDIOMYOPATHY (HCM) SUBPANEL
Hypertrophic Cardiomyopathy (HCM) is a commonly inherited monogenic cardiac disease with variable expression and age-related penetrance. HCM is a condition in which the myocardium is enlarged (hypertrophied) without an obvious cause. This hypertrophy is generally asymmetric and can be associated with obstruction of ventricular outflow. The most prevalent mutations in HCM occur among genes encoding sarcomere proteins. The clinical manifestations are highly variable, ranging from asymptomatic left ventricular hypertrophy to arrhythmias with atrial fibrillation, which is the most common sustained arrhythmia in HCM.
The Hypertrophic Cardiomyopathy (HCM) Subpanel contains the following 40 genes.
Gene MIM Disease Category OMIM Phenotype Inheritance
ACTC1
102540
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction
612794: AD Atrial septal defect 5 613424: AD Cardiomyopathy, dilated, 1R 612098: AD Cardiomyopathy, hypertrophic, 11 613424: AD Left ventricular noncompaction 4
AD
ACTN2
102573
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
612158: AD Cardiomyopathy, dilated, 1AA, with or without LVNC 612158: AD Cardiomyopathy, hypertrophic, 23, with or without LVNC
AD
AGL
610860 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Hypertrophic Cardiomyopathy; Metabolic Cardiomyopathy
232400: AR Glycogen storage disease IIIa 232400: AR Glycogen storage disease IIIb
AR
ANKRD1
609599
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
None
None
BAG3
603883
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
613881: AD Cardiomyopathy, dilated, 1HH 612954: AD Myopathy, myofibrillar, 6
AD
CACNA1C
114205
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Brugada Syndrome
611875: Brugada syndrome 3 601005: AD Timothy syndrome
AD
CAV3
601253
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
192600: AD Cardiomyopathy, familial hypertrophic 123320: AD Creatine phosphokinase, elevated serum 611818: AD Long QT syndrome 9 614321: AD Myopathy, distal, Tateyama type 606072: AD Rippling muscle disease
AD
CPT2
600650
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Hypertrophic Cardiomyopathy; Metabolic Cardiomyopathy
600649: AR CPT II deficiency, infantile 608836: AR CPT II deficiency, lethal neonatal 255110: AR, AD CPT II deficiency, myopathic, stress-induced 614212: AR, AD {Encephalopathy, acute, infection-induced, 4, susceptibility to}
AD, AR
CSRP3
600824
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
607482: ?Cardiomyopathy, dilated, 1M 612124: AD Cardiomyopathy, hypertrophic, 12
AD
DES
125660
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
604765: Cardiomyopathy, dilated, 1I 601419: AR, AD Myopathy, myofibrillar, 1 181400: AD Scapuloperoneal syndrome, neurogenic, Kaeser type
AD, AR
DMD
300377 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
300376: XLR Becker muscular dystrophy 302045: XL Cardiomyopathy, dilated, 3B 310200: XLR Duchenne muscular dystrophy
XLR, XL
FHL1
300163
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Hypertrophic Cardiomyopathy
300696: XLR Emery-Dreifuss muscular dystrophy 6, XL 300696: XLR Myopathy, XL, with postural muscle atrophy 300717: XLD Reducing body myopathy, XL 1a, severe, infantile or early childhood onset 300718: XL Reducing body myopathy, XL 1b, with late childhood or adult onset
XLD, XLR, XL
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
31 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
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Gene MIM Disease Category OMIM Phenotype Inheritance
300695: XLD Scapuloperoneal myopathy, XLD 300280: XLR ?Uruguay faciocardiomusculoskeletal syndrome
FLNC
102565
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
Cardiomyopathy, familial hypertrophic, 26 (3) 617047: AD Cardiomyopathy, familial restrictive 5 614065: AD Myopathy, distal, 4 609524: AD Myopathy, myofibrillar, 5
AD
GAA
606800
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Hypertrophic Cardiomyopathy; Metabolic Cardiomyopathy
232300: AR Glycogen storage disease II
AR
GLA
300644 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Hypertrophic Cardiomyopathy; Metabolic Cardiomyopathy
301500: XL Fabry disease 301500: XL Fabry disease, cardiac variant
XL
JPH2
605267
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Hypertrophic Cardiomyopathy
613873: AD Cardiomyopathy, hypertrophic, 17
AD
LAMP2
309060
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction; Metabolic Cardiomyopathy
300257: XLD Danon disease
XLD
LDB3
605906
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction
601493: AD Cardiomyopathy, dilated, 1C, with or without LVNC 601493: AD Cardiomyopathy, hypertrophic, 24 601493: AD Left ventricular noncompaction 3 609452: AD Myopathy, myofibrillar, 4
AD
MYBPC3
600958
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction
615396: AD Cardiomyopathy, dilated, 1MM 115197: AD Cardiomyopathy, hypertrophic, 4
615396: AD Left ventricular noncompaction 10
AD
MYH6
160710
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
614089: Atrial septal defect 3
613252: Cardiomyopathy, dilated, 1EE 613251: AD Cardiomyopathy, hypertrophic, 14 614090: {Sick sinus syndrome 3}
AD
MYH7
160760
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction
613426: AD Cardiomyopathy, dilated, 1S 192600: AD Cardiomyopathy, hypertrophic, 1 160500: AD Laing distal myopathy 613426: AD Left ventricular noncompaction 5 608358: AD Myopathy, myosin storage, AD 255160: AR Myopathy, myosin storage, AR 181430: AD Scapuloperoneal syndrome, myopathic type
AD, AR
MYL2
160781
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Hypertrophic Cardiomyopathy
608758: AD Cardiomyopathy, hypertrophic, 10
AD
MYL3
160790
Comprehensive Cardiovascular;
Comprehensive Cardiomyopathy; Hypertrophic Cardiomyopathy
608751: AR, AD Cardiomyopathy, hypertrophic, 8
AD, AR
MYLK2
606566 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Hypertrophic Cardiomyopathy
192600: AD Cardiomyopathy, hypertrophic, 1, digenic
AD
MYOM1
603508
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Hypertrophic Cardiomyopathy
None
None
MYOZ2
605602 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Hypertrophic Cardiomyopathy
613838: AD Cardiomyopathy, hypertrophic, 16
AD
MYPN
608517
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
615248: AD Cardiomyopathy, dilated, 1KK 615248: AD Cardiomyopathy, familial restrictive, 4 615248: AD Cardiomyopathy, hypertrophic, 22 617336: AR Nemaline myopathy 11, AR
AD, AR
NEXN
613121
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
613122: AD Cardiomyopathy, dilated, 1CC 613876: AD Cardiomyopathy, hypertrophic, 20
AD
PDLIM3 605889 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Hypertrophic
None None
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
32 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
Gene MIM Disease Category OMIM Phenotype Inheritance Cardiomyopathy
PLN
172405
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction
609909: Cardiomyopathy, dilated, 1P 613874: AD Cardiomyopathy, hypertrophic, 18
AD
PRKAG2
602743
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Hypertrophic Cardiomyopathy
600858: AD Cardiomyopathy, hypertrophic 6 261740: AD Glycogen storage disease of heart, lethal congenital 194200: ?AD Wolff-Parkinson-White syndrome
AD
PTPN11
176876
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Hypertrophic Cardiomyopathy; Noonan Spectrum Disorders
151100: AD LEOPARD syndrome 1 607785: Leukemia, juvenile myelomonocytic, somatic 156250: AD Metachondromatosis 163950: AD Noonan syndrome 1
AD
RAF1
164760
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Noonan Spectrum Disorders
615916: AD Cardiomyopathy, dilated, 1NN 611554: LEOPARD syndrome 2 611553: AD Noonan syndrome 5
AD
TCAP
604488 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
607487: AD Cardiomyopathy, hypertrophic, 25 601954: AR Muscular dystrophy, limb-girdle, AR 7
AD, AR
TNNC1
191040
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
611879: Cardiomyopathy, dilated, 1Z 613243: AD Cardiomyopathy, hypertrophic, 13
AD
TNNI3
191044
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction
613286: Cardiomyopathy, dilated, 1FF 611880: AR ?Cardiomyopathy, dilated, 2A 115210: AD Cardiomyopathy, familial restrictive, 1 613690: AD Cardiomyopathy, hypertrophic, 7
AD, AR
TNNT2
191045
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction
601494: AD Cardiomyopathy, dilated, 1D 612422: AD Cardiomyopathy, familial restrictive, 3 115195: AD Cardiomyopathy, hypertrophic, 2 601494: AD Left ventricular noncompaction 6
AD
TPM1
191010
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction
611878: AD Cardiomyopathy, dilated, 1Y 115196: AD Cardiomyopathy, hypertrophic, 3 611878: AD Left ventricular noncompaction 9
AD
TTR
176300
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
105210: AD Amyloidosis, hereditary, transthyretin-related 115430: AD Carpal tunnel syndrome, familial 145680: AD [Dystransthyretinemic hyperthyroxinemia]
AD
VCL
193065
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction
611407: Cardiomyopathy, dilated, 1W 613255: AD Cardiomyopathy, hypertrophic, 15
AD
1. Abbreviations: Autosomal Dominant (AD); Autosomal Recession (AR); Isolated Cases (IC); Multifactorial (MF); Somatic Mutations (SM;
Note: somatic mutations are not reported); XL (X-linked); XLD (X-linked Dominant); and XLR (X-linked Recessive). 2. DMD: The following DMD hg19 coordinates have been excluded from this assay: chrX:31897426-31897627, chrX:32668999-32669253,
chrX:32644476-32644680, chrX:31627637-31627838, chrX:32460213-32460334, chrX:31219361-31219367, chrX:31219126-31219287,
chrX:32644160-32644321
3. FLNC: The following FLNC hg19 coordinates have been excluded from this assay: chr7:128498050-128498282
4. LAMP2: The following LAMP2 hg19 coordinates have been excluded from this assay: chrX:119604075-119604081
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
33 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
LEFT VENTRICULAR NON-COMPACTION CARDIOMYOPATHY (LVNC) SUBPANEL
Left ventricular noncompaction cardiomyopathy (LVNC) is a congenital abnormality where the left ventricular myocardium fails to compact during embryonic development. The mechanism behind this disorder is thought to be an intrauterine arrest of myocardial development where pieces of muscle (trabeculations) fail to compact. The clinical presentation is variable and is associated with genetic heterogeneity. LVNC can range from asymptomatic to severe heart failure and sudden death. LVNC may occur in isolation or in association with congenital heart disease. LVNC also includes rhythm abnormalities including Wolff-Parkinson-White syndrome, conduction defects, and ventricular tachyarrhythmias. Higher occurrence of familial cases, facial dysmorphism, and congenital arrhythmias is observed in children.
The Left Ventricular Non-Compaction Cardiomyopathy (LVNC) Subpanel contains the following 20 genes.
Gene MIM Disease Category OMIM Phenotype Inheritance
ACTC1
102540
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction
612794: AD Atrial septal defect 5 613424: AD Cardiomyopathy, dilated, 1R 612098: AD Cardiomyopathy, hypertrophic, 11 613424: AD Left ventricular noncompaction 4
AD
DSP
125647
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Arrythmogenic Right Ventricular Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Left Ventricular Ncompaction
607450: AD Arrhythmogenic right ventricular dysplasia 8 605676: AR Cardiomyopathy, dilated, with woolly hair and keratoderma
615821: AD Dilated cardiomyopathy with woolly hair, keratoderma, and tooth agenesis 609638: AR Epidermolysis bullosa, lethal acantholytic 612908: AD Keratosis palmoplantaris striata II 607655: AR Skin fragility-woolly hair syndrome
AD, AR
DTNA
601239 Comprehensive Cardiovascular;
Comprehensive Cardiomyopathy; Left Ventricular Ncompaction
604169: AD Left ventricular noncompaction 1, with or without congenital heart defects
AD
HCN4
605206
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Left Ventricular Ncompaction; Brugada Syndrome
613123: Brugada syndrome 8 163800: AD Sick sinus syndrome 2
AD
LAMP2
309060
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction; Metabolic Cardiomyopathy
300257: XLD Danon disease
XLD
LDB3
605906
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction
601493: AD Cardiomyopathy, dilated, 1C, with or without LVNC 601493: AD Cardiomyopathy, hypertrophic, 24 601493: AD Left ventricular noncompaction 3 609452: AD Myopathy, myofibrillar, 4
AD
LMNA
150330
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Left Ventricular Ncompaction
115200: AD Cardiomyopathy, dilated, 1A 605588: AR Charcot-Marie-Tooth disease, type 2B1 181350: AD Emery-Dreifuss muscular dystrophy 2, AD 616516: AR Emery-Dreifuss muscular dystrophy 3, AR 610140: AD Heart-hand syndrome, Slovenian type 176670: AR, AD Hutchinson-Gilford progeria 151660: AD Lipodystrophy, familial partial, type 2 212112: AD Malouf syndrome 248370: AR Mandibuloacral dysplasia 613205: AD Muscular dystrophy, congenital 275210: AR Restrictive dermopathy, lethal
AD, AR
MIB1 608677 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Left
615092: AD Left ventricular noncompaction 7 AD
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
34 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
Gene MIM Disease Category OMIM Phenotype Inheritance Ventricular Ncompaction
MYBPC3
600958
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction
615396: AD Cardiomyopathy, dilated, 1MM 115197: AD Cardiomyopathy, hypertrophic, 4 615396: AD Left ventricular noncompaction 10
AD
MYH7
160760
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction
613426: AD Cardiomyopathy, dilated, 1S 192600: AD Cardiomyopathy, hypertrophic, 1 160500: AD Laing distal myopathy 613426: AD Left ventricular noncompaction 5 608358: AD Myopathy, myosin storage, AD 255160: AR Myopathy, myosin storage, AR 181430: AD Scapuloperoneal syndrome, myopathic type
AD, AR
PLEKHM2
609613
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Left Ventricular Ncompaction
None
None
PLN
172405
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction
609909: Cardiomyopathy, dilated, 1P 613874: AD Cardiomyopathy, hypertrophic, 18
AD
PRDM16
605557 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Left Ventricular Ncompaction
615373: AD Cardiomyopathy, dilated, 1LL 615373: AD Left ventricular noncompaction 8
AD
RYR2
180902
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Catecholaminergic Polymorphic Ventricular Tachycardia; Arrythmogenic Right Ventricular Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Left Ventricular Ncompaction
600996: AD Arrhythmogenic right ventricular dysplasia 2 604772: AD Ventricular tachycardia, catecholaminergic polymorphic, 1
AD
SCN5A
600163
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias; Dilated Cardiomyopathy; Left Ventricular Ncompaction; Brugada Syndrome
614022: AD Atrial fibrillation, familial, 10
601144: AD Brugada syndrome 1 601154: AD Cardiomyopathy, dilated, 1E 113900: AD Heart block, nonprogressive 113900: AD Heart block, progressive, type IA 603830: AD Long QT syndrome-3 608567: AR Sick sinus syndrome 1 272120: AR {Sudden infant death syndrome, susceptibility to} 603829: Ventricular fibrillation, familial, 1
AD, AR
TAZ
300394
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Left Ventricular Ncompaction; Metabolic Cardiomyopathy
302060: XLR Barth syndrome
XLR
TNNI3
191044
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction
613286: Cardiomyopathy, dilated, 1FF 611880: AR ?Cardiomyopathy, dilated, 2A 115210: AD Cardiomyopathy, familial restrictive, 1 613690: AD Cardiomyopathy, hypertrophic, 7
AD, AR
TNNT2
191045
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction
601494: AD Cardiomyopathy, dilated, 1D 612422: AD Cardiomyopathy, familial restrictive, 3 115195: AD Cardiomyopathy, hypertrophic, 2 601494: AD Left ventricular noncompaction 6
AD
TPM1
191010
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction
611878: AD Cardiomyopathy, dilated, 1Y 115196: AD Cardiomyopathy, hypertrophic, 3 611878: AD Left ventricular noncompaction 9
AD
VCL
193065
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction
611407: Cardiomyopathy, dilated, 1W 613255: AD Cardiomyopathy, hypertrophic, 15
AD
1. Abbreviations: Autosomal Dominant (AD); Autosomal Recession (AR); Isolated Cases (IC); Multifactorial (MF); Somatic Mutations (SM; Note: somatic mutations are not reported); XL (X-linked); XLD (X-linked Dominant); and XLR (X-linked Recessive).
2. LAMP2: The following LAMP2 hg19 coordinates have been excluded from this assay: chrX:119604075-119604081
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
35 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
THE COMPREHENSIVE ARRHYTHMIAS PANEL
Collectively, arrhythmias are disorders of cardiac ion channels and are commonly referred to as cardiac channelopathies. The maintenance of normal cardiac rhythm depends on the proper movement of ions mediating the action potential in each cardiac compartment. In arrhythmias, abnormalities in ion channel function manifest as electrocardiogram abnormalities and in most studies, individuals who are digenic/biallelic carriers have a more severe arrhythmia phenotype. Pathogenic variants in certain genes, which encode specific ion channels, have been shown to underlie well known heritable arrhythmogenic disorders occurring in the structurally normal heart. These include arrhythmogenic right ventricular cardiomyopathy, long and short QT syndromes, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia (CPVT). The Arrhythmias Panel contains the following 54 genes with four well-established subpanels: Arrythmogenic Right Ventricular Cardiomyopathy (ARVC), Brugada Syndrome (BrS), CPVT, and Long / Short QT Syndrome (LSQT).
Gene MIM Disease Category OMIM Phenotype Inheritance
ABCC9
601439
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Brugada Syndrome
614050: AD Atrial fibrillation, familial, 12 608569: Cardiomyopathy, dilated, 1O 239850: AD Hypertrichotic osteochondrodysplasia
AD
ACTN2
102573
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
612158: AD Cardiomyopathy, dilated, 1AA, with or without LVNC 612158: AD Cardiomyopathy, hypertrophic, 23, with or without LVNC
AD
AKAP9
604001
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias;
611820: AD ?Long QT syndrome-11
AD
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
36 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
Gene MIM Disease Category OMIM Phenotype Inheritance Dilated Cardiomyopathy
ANK2
106410
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Catecholaminergic Polymorphic Ventricular Tachycardia; Long / Short Qt Syndrome; Comprehensive Arrythmias; Dilated Cardiomyopathy
600919: AD Cardiac arrhythmia, ankyrin-B- related 600919: AD Long QT syndrome 4
AD
CACNA1C
114205
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Brugada Syndrome
611875: Brugada syndrome 3 601005: AD Timothy syndrome
AD
CACNA2D1
114204
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias; Brugada Syndrome
None
None
CACNB2
600003
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias; Brugada Syndrome
611876: Brugada syndrome 4
None
CALM1
114180
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Catecholaminergic Polymorphic Ventricular Tachycardia; Long / Short Qt Syndrome; Comprehensive Arrythmias
616247: AD Long QT syndrome 14 614916: AD Ventricular tachycardia, catecholaminergic polymorphic, 4
AD
CALM2
114182
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Catecholaminergic Polymorphic Ventricular Tachycardia; Long / Short Qt Syndrome; Comprehensive Arrythmias
616249: AD Long QT syndrome 15
AD
CALM3
114183
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Catecholaminergic Polymorphic Ventricular Tachycardia; Long / Short Qt Syndrome; Comprehensive Arrythmias
None
None
CASQ2
114251
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Catecholaminergic Polymorphic Ventricular Tachycardia; Comprehensive Arrythmias
611938: AR Ventricular tachycardia, catecholaminergic polymorphic, 2
AR
CAV3
601253
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
192600: AD Cardiomyopathy, familial hypertrophic 123320: AD Creatine phosphokinase, elevated serum
611818: AD Long QT syndrome 9 614321: AD Myopathy, distal, Tateyama type 606072: AD Rippling muscle disease
AD
CTNNA3
607667
Comprehensive Cardiovascular;
Comprehensive Cardiomyopathy; Comprehensive Arrythmias
615616: AD Arrhythmogenic right ventricular dysplasia, familial, 13
AD
DES
125660
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
604765: Cardiomyopathy, dilated, 1I 601419: AR, AD Myopathy, myofibrillar, 1 181400: AD Scapuloperoneal syndrome, neurogenic, Kaeser type
AD, AR
DSC2
125645
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Arrythmogenic Right Ventricular Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy
610476: AR, AD Arrhythmogenic right ventricular dysplasia 11 610476: AR, AD Arrhythmogenic right ventricular dysplasia 11 with mild palmoplantar keratoderma and woolly hair
AD, AR
DSG2
125671
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Arrythmogenic Right Ventricular Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy
610193: AD Arrhythmogenic right ventricular dysplasia 10 612877: Cardiomyopathy, dilated, 1BB
AD
DSP
125647
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Arrythmogenic Right Ventricular
Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Left Ventricular
607450: AD Arrhythmogenic right ventricular dysplasia 8 605676: AR Cardiomyopathy, dilated, with woolly hair and keratoderma 615821: AD Dilated cardiomyopathy with woolly
AD, AR
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
37 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
Gene MIM Disease Category OMIM Phenotype Inheritance
Ncompaction hair, keratoderma, and tooth agenesis 609638: AR Epidermolysis bullosa, lethal acantholytic 612908: AD Keratosis palmoplantaris striata II 607655: AR Skin fragility-woolly hair syndrome
EMD
300384
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy
310300: XLR Emery-Dreifuss muscular dystrophy 1, XL
XLR, XL
GJA5
121013
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias
614049: AD Atrial fibrillation, familial, 11 108770: AD Atrial standstill, digenic (GJA5/SCN5A)
AD
GPD1L
611778
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Brugada Syndrome
611777: Brugada syndrome 2
None
HCN4
605206
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Left Ventricular Ncompaction; Brugada Syndrome
613123: Brugada syndrome 8 163800: AD Sick sinus syndrome 2
AD
JUP
173325
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Arrythmogenic Right Ventricular Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy
611528: AD Arrhythmogenic right ventricular dysplasia 12 601214: AR Naxos disease
AD, AR
KCNA5
176267
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Pulmonary Hypertension
612240: AD Atrial fibrillation, familial, 7
AD
KCND3
605411
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Brugada Syndrome
616399: AD Brugada syndrome 9 607346: AD Spinocerebellar ataxia 19
AD
KCNE1
176261
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias
612347: AR Jervell and Lange-Nielsen syndrome 2 613695: AD Long QT syndrome 5
AD, AR
KCNE2
603796 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias
611493: Atrial fibrillation, familial, 4 613693: AD Long QT syndrome 6
AD
KCNE3
604433
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Brugada Syndrome
613119: Brugada syndrome 6
None
KCNE5
300328
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Brugada Syndrome
None
None
KCNH2
152427
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias; Brugada Syndrome
613688: AD Long QT syndrome 2 613688: AD {Long QT syndrome 2, acquired, susceptibility to} 609620: Short QT syndrome 1
AD
KCNJ2
600681
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Catecholaminergic Polymorphic Ventricular Tachycardia; Long / Short Qt Syndrome; Comprehensive Arrythmias
170390: AD Andersen syndrome 613980: AD Atrial fibrillation, familial, 9 609622: Short QT syndrome 3
AD
KCNJ5
600734
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias
613677: AD Hyperaldosteronism, familial, type III 613485: AD Long QT syndrome 13
AD
KCNJ8
600935
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Brugada Syndrome
None
None
KCNQ1
607542
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias
607554: AD Atrial fibrillation, familial, 3 220400: AR Jervell and Lange-Nielsen syndrome
192500: AD Long QT syndrome 1 192500: AD {Long QT syndrome 1, acquired,
AD, AR
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
38 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
Gene MIM Disease Category OMIM Phenotype Inheritance
susceptibility to} 609621: AD Short QT syndrome 2
LDB3
605906
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction
601493: AD Cardiomyopathy, dilated, 1C, with or without LVNC 601493: AD Cardiomyopathy, hypertrophic, 24 601493: AD Left ventricular noncompaction 3 609452: AD Myopathy, myofibrillar, 4
AD
LMNA
150330
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Left Ventricular Ncompaction
115200: AD Cardiomyopathy, dilated, 1A 605588: AR Charcot-Marie-Tooth disease, type 2B1 181350: AD Emery-Dreifuss muscular dystrophy 2, AD
616516: AR Emery-Dreifuss muscular dystrophy 3, AR 610140: AD Heart-hand syndrome, Slovenian type 176670: AR, AD Hutchinson-Gilford progeria 151660: AD Lipodystrophy, familial partial, type 2 212112: AD Malouf syndrome 248370: AR Mandibuloacral dysplasia 613205: AD Muscular dystrophy, congenital 275210: AR Restrictive dermopathy, lethal
AD, AR
NKX2-5
600584
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Congenital Heart Disease
108900: AD Atrial septal defect 7, with or without AV conduction defects 217095: Conotruncal heart malformations, variable 614435: AD Hypoplastic left heart syndrome 2 225250: AD Hypothyroidism, congenital nongoitrous, 5
187500: AD Tetralogy of Fallot 614432: AD Ventricular septal defect 3
AD
NPPA
108780 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias
612201: AD Atrial fibrillation, familial, 6 615745: AR Atrial standstill 2
AD, AR
PKP2
602861
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Arrythmogenic Right Ventricular Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Brugada Syndrome
609040: AD Arrhythmogenic right ventricular dysplasia 9
AD
PLN
172405
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction
609909: Cardiomyopathy, dilated, 1P 613874: AD Cardiomyopathy, hypertrophic, 18
AD
PRKAG2
602743
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Hypertrophic Cardiomyopathy
600858: AD Cardiomyopathy, hypertrophic 6 261740: AD Glycogen storage disease of heart, lethal congenital 194200: ?AD Wolff-Parkinson-White syndrome
AD
RANGRF
607954
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Brugada Syndrome
None
None
RYR2
180902
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Catecholaminergic Polymorphic Ventricular Tachycardia; Arrythmogenic Right Ventricular Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Left Ventricular Ncompaction
600996: AD Arrhythmogenic right ventricular dysplasia 2 604772: AD Ventricular tachycardia, catecholaminergic polymorphic, 1
AD
SCN10A
604427
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Brugada Syndrome
615551: AD Episodic pain syndrome, familial, 2
AD
SCN1B
600235
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Brugada Syndrome
615377: AD Atrial fibrillation, familial, 13 612838: Brugada syndrome 5
612838: Cardiac conduction defect, nonspecific 604233: AD Epilepsy, generalized, with febrile
AD, AR
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
39 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
Gene MIM Disease Category OMIM Phenotype Inheritance
seizures plus, type 1 617350: AR Epileptic encephalopathy, early infantile, 52
SCN2B
601327
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Brugada Syndrome
615378: AD Atrial fibrillation, familial, 14
AD
SCN3B
608214
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Brugada Syndrome
613120: AD Atrial fibrillation, familial, 16 613120: AD Brugada syndrome 7
AD
SCN4B
608256 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias
611819: AD Atrial fibrillation, familial, 17 611819: AD Long QT syndrome-10
AD
SCN5A
600163
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias; Dilated Cardiomyopathy; Left Ventricular Ncompaction; Brugada Syndrome
614022: AD Atrial fibrillation, familial, 10 601144: AD Brugada syndrome 1 601154: AD Cardiomyopathy, dilated, 1E 113900: AD Heart block, nonprogressive 113900: AD Heart block, progressive, type IA 603830: AD Long QT syndrome-3 608567: AR Sick sinus syndrome 1 272120: AR {Sudden infant death syndrome, susceptibility to} 603829: Ventricular fibrillation, familial, 1
AD, AR
SLMAP
602701
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Brugada Syndrome
None
None
SNTA1
601017
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias
612955: AD Long QT syndrome 12
AD
TGFB3
190230
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Arrythmogenic Right Ventricular Cardiomyopathy; Aortopathies; Comprehensive Arrythmias
107970: AD Arrhythmogenic right ventricular dysplasia 1 615582: AD Loeys-Dietz syndrome 5
AD
TMEM43
612048
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Arrythmogenic Right Ventricular Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy
604400: AD Arrhythmogenic right ventricular dysplasia 5 614302: AD Emery-Dreifuss muscular dystrophy 7, AD
AD
TRDN
603283
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Catecholaminergic Polymorphic Ventricular Tachycardia; Long / Short Qt Syndrome; Comprehensive Arrythmias
615441: AR Ventricular tachycardia, catecholaminergic polymorphic, 5, with or without muscle weakness
AR
TRPM4
606936
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Brugada Syndrome
604559: AD Progressive familial heart block, type IB
AD
1. Abbreviations: Autosomal Dominant (AD); Autosomal Recession (AR); Isolated Cases (IC); Multifactorial (MF); Somatic Mutations (SM;
Note: somatic mutations are not reported); XL (X-linked); XLD (X-linked Dominant); and XLR (X-linked Recessive).
2. SCN1B: The following SCN1B hg19 coordinates have been excluded from this assay: chr19:35521713-35521775
3. TRDN: The following TRDN hg19 coordinates have been excluded from this assay: chr6:123851639-123851721, chr6:123576214- 123576281
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
40 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
BRUGADA SYNDROME (BrS) SUBPANEL
Brugada syndrome (BrS) is a channelopathy caused by genetic changes in transmembrane ion channels and cardiac conduction abnormalities that can result in sudden death. BrS is typically associated with a distinctive electrocardiogram (ECG) pattern in the absence of structural heart abnormalities. Of note, malignant arrhythmias and a previous history of syncopal episodes is a common presentation. Specifically, there is a ST-segment elevation in BrS within the right precordial ECG leads. The ST-segment elevation may be transient in nature and can be evoked by pharmacological sodium channel blockade. Other conduction defects can manifest as first- degree AV block, intraventricular conduction delay, right bundle branch block, and sick sinus syndrome. Loss-of- function mutations in the pore-forming subunit of the cardiac sodium channel have been causally related to the disease in a subset of cases. Although BrS is commonly considered a Mendelian disorder with autosomal dominant transmission, studies in families harboring BrS-related mutations have demonstrated low disease penetrance and, in some instances, absence of a familial mutation in some affected family members. An implantable cardioverter defibrillator is recommended for management of individuals with a history of syncope or cardiac arrest.
The Brugada Syndrome (BrS) Subpanel contains the following 20 genes.
Gene MIM Disease Category OMIM Phenotype Inheritance
ABCC9
601439
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Brugada Syndrome
614050: AD Atrial fibrillation, familial, 12 608569: Cardiomyopathy, dilated, 1O 239850: AD Hypertrichotic osteochondrodysplasia
AD
CACNA1C
114205
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Brugada Syndrome
611875: Brugada syndrome 3 601005: AD Timothy syndrome
AD
CACNA2D1
114204
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias; Brugada Syndrome
None
None
CACNB2
600003
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias; Brugada Syndrome
611876: Brugada syndrome 4
None
GPD1L
611778
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Brugada Syndrome
611777: Brugada syndrome 2
None
HCN4
605206
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Left Ventricular Ncompaction; Brugada Syndrome
613123: Brugada syndrome 8 163800: AD Sick sinus syndrome 2
AD
KCND3
605411
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Brugada Syndrome
616399: AD Brugada syndrome 9 607346: AD Spinocerebellar ataxia 19
AD
KCNE3
604433
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Brugada Syndrome
613119: Brugada syndrome 6
None
KCNE5
300328
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Brugada Syndrome
None
None
KCNH2
152427
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias; Brugada Syndrome
613688: AD Long QT syndrome 2 613688: AD {Long QT syndrome 2, acquired, susceptibility to} 609620: Short QT syndrome 1
AD
KCNJ8
600935
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Brugada Syndrome
None
None
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
41 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
Gene MIM Disease Category OMIM Phenotype Inheritance
PKP2
602861
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Arrythmogenic Right Ventricular Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Brugada Syndrome
609040: AD Arrhythmogenic right ventricular dysplasia 9
AD
RANGRF
607954
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Brugada Syndrome
None
None
SCN10A
604427
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Brugada Syndrome
615551: AD Episodic pain syndrome, familial, 2
AD
SCN1B
600235
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Brugada Syndrome
615377: AD Atrial fibrillation, familial, 13 612838: Brugada syndrome 5 612838: Cardiac conduction defect, nonspecific 604233: AD Epilepsy, generalized, with febrile seizures plus, type 1 617350: AR Epileptic encephalopathy, early infantile, 52
AD, AR
SCN2B
601327
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Brugada Syndrome
615378: AD Atrial fibrillation, familial, 14
AD
SCN3B
608214
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Brugada Syndrome
613120: AD Atrial fibrillation, familial, 16 613120: AD Brugada syndrome 7
AD
SCN5A
600163
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias; Dilated Cardiomyopathy; Left Ventricular Ncompaction; Brugada Syndrome
614022: AD Atrial fibrillation, familial, 10 601144: AD Brugada syndrome 1 601154: AD Cardiomyopathy, dilated, 1E 113900: AD Heart block, nonprogressive
113900: AD Heart block, progressive, type IA 603830: AD Long QT syndrome-3 608567: AR Sick sinus syndrome 1 272120: AR {Sudden infant death syndrome, susceptibility to} 603829: Ventricular fibrillation, familial, 1
AD, AR
SLMAP
602701
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Brugada Syndrome
None
None
TRPM4
606936
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Brugada Syndrome
604559: AD Progressive familial heart block, type IB
AD
1. Abbreviations: Autosomal Dominant (AD); Autosomal Recession (AR); Isolated Cases (IC); Multifactorial (MF); Somatic Mutations (SM; Note: somatic mutations are not reported); XL (X-linked); XLD (X-linked Dominant); and XLR (X-linked Recessive).
2. SCN1B: The following SCN1B hg19 coordinates have been excluded from this assay: chr19:35521713-35521775
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
42 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
treatment with β‐
‐
CATECHOLAMINERGIC POLYMORPHIC VENTRICULAR TACHYCARDIA (CPVT) SUBPANEL
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited life threatening arrhythmia leading to syncope and sudden cardiac death at a young age. CPVT patients do not show any detectable cardiac disease
and in particular manifest ventricular premature beats and bidirectional or polymorphic ventricular tachycardia in response to emotional or physical stress. Spontaneous recovery may occur when these arrhythmias self-
terminate. However, in other instances, the ventricular tachycardia can degenerate into ventricular fibrillation and cause sudden death if cardiopulmonary resuscitation (CPR) is not performed. The common genetic form of CPVT is associated with autosomal dominant mutations in the cardiac ryanodine receptor, however there is also a very
rare form linked to recessive mutations in calsequestrin. Current clinical management of CPVT is based on blockers to reduce the frequency of arrhythmias and the implantation of automated defibrillators
to terminate fatal arrhythmias.
The Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) Subpanel contains the following 8 genes.
Gene MIM Disease Category OMIM Phenotype Inheritance
ANK2
106410
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Catecholaminergic Polymorphic Ventricular Tachycardia; Long / Short Qt Syndrome; Comprehensive Arrythmias; Dilated Cardiomyopathy
600919: AD Cardiac arrhythmia, ankyrin-B- related
600919: AD Long QT syndrome 4
AD
CALM1
114180
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Catecholaminergic Polymorphic Ventricular Tachycardia; Long / Short Qt Syndrome; Comprehensive Arrythmias
616247: AD Long QT syndrome 14 614916: AD Ventricular tachycardia, catecholaminergic polymorphic, 4
AD
CALM2
114182
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Catecholaminergic Polymorphic Ventricular Tachycardia; Long / Short Qt Syndrome; Comprehensive Arrythmias
616249: AD Long QT syndrome 15
AD
CALM3
114183
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Catecholaminergic Polymorphic Ventricular
Tachycardia; Long / Short Qt Syndrome; Comprehensive Arrythmias
None
None
CASQ2
114251
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Catecholaminergic Polymorphic Ventricular Tachycardia; Comprehensive Arrythmias
611938: AR Ventricular tachycardia, catecholaminergic polymorphic, 2
AR
KCNJ2
600681
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Catecholaminergic Polymorphic Ventricular Tachycardia; Long / Short Qt Syndrome; Comprehensive Arrythmias
170390: AD Andersen syndrome 613980: AD Atrial fibrillation, familial, 9 609622: Short QT syndrome 3
AD
RYR2
180902
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Catecholaminergic Polymorphic Ventricular Tachycardia; Arrythmogenic Right Ventricular Cardiomyopathy; Comprehensive Arrythmias; Dilated Cardiomyopathy; Left Ventricular Ncompaction
600996: AD Arrhythmogenic right ventricular dysplasia 2 604772: AD Ventricular tachycardia, catecholaminergic polymorphic, 1
AD
TRDN
603283
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Catecholaminergic Polymorphic Ventricular Tachycardia; Long / Short Qt Syndrome; Comprehensive Arrythmias
615441: AR Ventricular tachycardia, catecholaminergic polymorphic, 5, with or without muscle weakness
AR
1. Abbreviations: Autosomal Dominant (AD); Autosomal Recession (AR); Isolated Cases (IC); Multifactorial (MF); Somatic Mutations (SM; Note: somatic mutations are not reported); XL (X-linked); XLD (X-linked Dominant); and XLR (X-linked Recessive).
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
43 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
2. TRDN: The following TRDN hg19 coordinates have been excluded from this assay: chr6:123851639-123851721, chr6:123576214- 123576281
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
44 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
Treatment options typically involve β‐
LONG / SHORT QT SYNDROME (LQTS / SQTS) SUBPANEL
Inherited arrhythmias such as long QT syndrome (LQTS) or short QT syndrome (SQTS) occur in a heterogeneous collection of Mendelian disorders, often leading to sudden cardiac death. These disorders are usually caused by rare, highly penetrant mutations in ion channel genes. LQTS is characterized by a prolongation of the QT interval and T-wave abnormalities on electrocardiograms along with a propensity to ventricular tachyarrhythmias, which lead to syncope and/or cardiac arrest. The fundamental arrhythmogenic triggering mechanisms are linked to the decreased outward potassium currents in LQTS. In contrast, SQTS is characterized by a short QT interval with the late portion of the T-wave being statistically prolonged in most SQTS reports. Individuals with SQTS may manifest symptoms such as syncope, cardiac arrest, atrial fibrillation, idiopathic ventricular fibrillation, bradycardia and irregular rhythm. However, for both syndromes, an abnormal QT interval is not always associated with an increased risk of cardiac events since a wide range of QT intervals are considered abnormal without a significant increase in risk. Additional risk factors can include administration of certain medications such as antidepressants or cholesterol-lowering drugs that can exacerbate the QT interval profile.
blockers and implantable cardioverter-defibrillators as therapeutic options to
prevent cardiac arrest.
The Long / Short QT Syndrome Subpanel contains the following 19 genes.
Gene MIM Disease Category OMIM Phenotype Inheritance
AKAP9
604001
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias; Dilated Cardiomyopathy
611820: AD ?Long QT syndrome-11
AD
ANK2
106410
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Catecholaminergic Polymorphic Ventricular Tachycardia; Long / Short Qt Syndrome; Comprehensive Arrythmias; Dilated Cardiomyopathy
600919: AD Cardiac arrhythmia, ankyrin-B- related 600919: AD Long QT syndrome 4
AD
CACNA1C
114205
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Brugada Syndrome
611875: Brugada syndrome 3 601005: AD Timothy syndrome
AD
CACNA2D1
114204
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias; Brugada Syndrome
None
None
CACNB2
600003
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias; Brugada Syndrome
611876: Brugada syndrome 4
None
CALM1
114180
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Catecholaminergic Polymorphic Ventricular Tachycardia; Long / Short Qt Syndrome; Comprehensive Arrythmias
616247: AD Long QT syndrome 14 614916: AD Ventricular tachycardia, catecholaminergic polymorphic, 4
AD
CALM2
114182
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Catecholaminergic Polymorphic Ventricular Tachycardia; Long / Short Qt Syndrome; Comprehensive Arrythmias
616249: AD Long QT syndrome 15
AD
CALM3
114183
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Catecholaminergic Polymorphic Ventricular Tachycardia; Long / Short Qt Syndrome; Comprehensive Arrythmias
None
None
CAV3
601253
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
192600: AD Cardiomyopathy, familial hypertrophic 123320: AD Creatine phosphokinase, elevated serum 611818: AD Long QT syndrome 9 614321: AD Myopathy, distal, Tateyama type
AD
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
45 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
Gene MIM Disease Category OMIM Phenotype Inheritance 606072: AD Rippling muscle disease
KCNE1
176261 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias
612347: AR Jervell and Lange-Nielsen syndrome 2 613695: AD Long QT syndrome 5
AD, AR
KCNE2
603796
Comprehensive Cardiovascular;
Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias
611493: Atrial fibrillation, familial, 4 613693: AD Long QT syndrome 6
AD
KCNH2
152427
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias; Brugada Syndrome
613688: AD Long QT syndrome 2
613688: AD {Long QT syndrome 2, acquired, susceptibility to} 609620: Short QT syndrome 1
AD
KCNJ2
600681
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Catecholaminergic Polymorphic Ventricular Tachycardia; Long / Short Qt Syndrome; Comprehensive Arrythmias
170390: AD Andersen syndrome 613980: AD Atrial fibrillation, familial, 9
609622: Short QT syndrome 3
AD
KCNJ5
600734 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias
613677: AD Hyperaldosteronism, familial, type III 613485: AD Long QT syndrome 13
AD
KCNQ1
607542
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias
607554: AD Atrial fibrillation, familial, 3 220400: AR Jervell and Lange-Nielsen syndrome
192500: AD Long QT syndrome 1 192500: AD {Long QT syndrome 1, acquired, susceptibility to} 609621: AD Short QT syndrome 2
AD, AR
SCN4B
608256 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias
611819: AD Atrial fibrillation, familial, 17 611819: AD Long QT syndrome-10
AD
SCN5A
600163
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias; Dilated Cardiomyopathy; Left Ventricular Ncompaction; Brugada Syndrome
614022: AD Atrial fibrillation, familial, 10 601144: AD Brugada syndrome 1 601154: AD Cardiomyopathy, dilated, 1E 113900: AD Heart block, nonprogressive 113900: AD Heart block, progressive, type IA 603830: AD Long QT syndrome-3 608567: AR Sick sinus syndrome 1
272120: AR {Sudden infant death syndrome, susceptibility to} 603829: Ventricular fibrillation, familial, 1
AD, AR
SNTA1
601017 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Long / Short Qt Syndrome; Comprehensive Arrythmias
612955: AD Long QT syndrome 12
AD
TRDN
603283
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Catecholaminergic Polymorphic Ventricular Tachycardia; Long / Short Qt Syndrome; Comprehensive Arrythmias
615441: AR Ventricular tachycardia, catecholaminergic polymorphic, 5, with or without muscle weakness
AR
1. Abbreviations: Autosomal Dominant (AD); Autosomal Recession (AR); Isolated Cases (IC); Multifactorial (MF); Somatic Mutations (SM;
Note: somatic mutations are not reported); XL (X-linked); XLD (X-linked Dominant); and XLR (X-linked Recessive). 2. TRDN: The following TRDN hg19 coordinates have been excluded from this assay: chr6:123851639-123851721, chr6:123576214-
123576281
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
46 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
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AORTOPATHIES PANEL
Aortopathies account for a significant healthcare burden that is likely underestimated and underdiagnosed due to early mortality caused by aneurysms. Typically, aortopathies are subcategorized into thoracic abdominal aortic aneurysm and abdominal aortic aneurysm. Abdominal aortic aneurysms are common degenerative disorders associated with traditional atherosclerotic risk factors such as advanced age, cigarette smoking, hypertension, and hypercholesterolemia. These aneurysms tend to arise from complicated interactions of multiple predisposing genes and environmental risk factors. By contrast, thoracic abdominal aneurysms occur across all age groups and can present as part of a genetic syndrome or an isolated anomaly. Most genetic causes of heritable aortopathies are transmitted as monogenic defects with autosomal dominant patterns of inheritance associated with high penetrance. Notably, since clinical variability between and within genetic subtypes is a hallmark of aortic disease, next-generation sequencing is a robust method to delineate loci associated with the hereditary aortopathies.
The Aortopathies Panel contains the following 33 genes.
Gene MIM Disease Category OMIM Phenotype Inheritance
ACTA2
102620
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies
611788: AD Aortic aneurysm, familial thoracic 6 614042: Moyamoya disease 5 613834: AD Multisystemic smooth muscle dysfunction syndrome
AD
ADAMTS2 604539 Comprehensive Cardiovascular; Aortopathies 225410: AR Ehlers-Danlos syndrome, dermatosparaxis type
AR
ATP7A
300011
Comprehensive Cardiovascular; Aortopathies
309400: XLR Menkes disease 304150: XLR Occipital horn syndrome 300489: XLR Spinal muscular atrophy, distal, XL 3
XLR, XL
CBS
613381
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies
236200: AR Homocystinuria, B6-responsive and nonresponsive types 236200: AR Thrombosis, hyperhomocysteinemic
AR
CHST14 608429 Comprehensive Cardiovascular; Aortopathies 601776: AR Ehlers-Danlos syndrome, musculocontractural type 1
AR
COL1A1
120150
Comprehensive Cardiovascular; Aortopathies
166710: AD {Bone mineral density variation QTL, osteoporosis} 114000: AD Caffey disease 130060: AD Ehlers-Danlos syndrome, arthrochalasia type, 1 166200: AD Osteogenesis imperfecta, type I 166210: AD Osteogenesis imperfecta, type II 259420: AD Osteogenesis imperfecta, type III 166220: AD Osteogenesis imperfecta, type IV
AD
COL1A2
120160
Comprehensive Cardiovascular; Aortopathies
617821: AD Ehlers-Danlos syndrome, arthrochalasia type, 2 225320: AR Ehlers-Danlos syndrome, cardiac valvular type 259420: AD imperfecta, type III 166210: AD Osteogenesis imperfecta, type II 166220: AD Osteogenesis imperfecta, type IV 166710: AD {Osteoporosis, postmenopausal}
AD, AR
COL3A1 120180 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies
130050: AD Ehlers-Danlos syndrome, vascular type
AD
COL5A1 120215 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies
130000: AD Ehlers-Danlos syndrome, classic type, 1 AD
COL5A2 120190 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies
130010: AD Ehlers-Danlos syndrome, classic type, 2
AD
EFEMP2 604633 Comprehensive Cardiovascular; Aortopathies 614437: AR Cutis laxa, AR, type IB AR
FBN1
134797
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies
102370: AD Acromicric dysplasia 129600: AD Ectopia lentis, familial 614185: AD Geleophysic dysplasia 2 604308: MASS syndrome
AD
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
47 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
Gene MIM Disease Category OMIM Phenotype Inheritance
616914: AD Marfan lipodystrophy syndrome 154700: AD Marfan syndrome 184900: AD Stiff skin syndrome 608328: AD Weill-Marchesani syndrome 2, dominant
FBN2
612570 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies
121050: AD Contractural arachnodactyly, congenital 616118: AD Macular degeneration, early-onset
AD
FKBP14 614505 Comprehensive Cardiovascular; Aortopathies 614557: AR Ehlers-Danlos syndrome, kyphoscoliotic type, 2
AR
FLNA
300017
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies
314400: XLR Cardiac valvular dysplasia, XL 300048: XLR Congenital short bowel syndrome 300321: XL ?FG syndrome 2 305620: XLR Frontometaphyseal dysplasia 1 300049: XLD Heterotopia, periventricular 300048: XLR Intestinal pseudoobstruction, neuronal 309350: XLD Melnick-Needles syndrome 311300: XLD Otopalatodigital syndrome, type I 304120: XLD Otopalatodigital syndrome, type II 300244: XLD Terminal osseous dysplasia
XLD, XLR, XL
MAT2A 601468 Comprehensive Cardiovascular; Aortopathies None None
MED12
300188
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies
309520: XLR Lujan-Fryns syndrome 300895: XLR Ohdo syndrome, XL 305450: XLR Opitz-Kaveggia syndrome
XLR, XL
MFAP5 601103 Comprehensive Cardiovascular; Aortopathies 616166: AD Aortic aneurysm, familial thoracic 9 AD
MYH11 160745 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies 132900: AD Aortic aneurysm, familial thoracic 4 AD
MYLK 600922 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies
613780: AD Aortic aneurysm, familial thoracic 7 AD
NOTCH1
190198 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies; Congenital Heart Disease
616028: AD Adams-Oliver syndrome 5 109730: AD Aortic valve disease 1
AD
PLOD1 153454 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies
225400: AR Ehlers-Danlos syndrome, kyphoscoliotic type, 1
AR
PRKG1 176894 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies 615436: AD Aortic aneurysm, familial thoracic 8 AD
SKI 164780 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies
182212: AD Shprintzen-Goldberg syndrome AD
SLC2A10 606145 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies
208050: AR Arterial tortuosity syndrome AR
SLC39A13 608735 Comprehensive Cardiovascular; Aortopathies 612350: AR Ehlers-Danlos syndrome, spondylodysplastic type, 3
AR
SMAD3 603109 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies
613795: AD Loeys-Dietz syndrome 3 AD
SMAD4
600993
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies; Hereditary Hemorrhagic Telangiectasia
175050: AD Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome 139210: AD Myhre syndrome 260350: Pancreatic cancer, somatic 174900: AD Polyposis, juvenile intestinal
AD
SMAD6
602931 Comprehensive Cardiovascular; Aortopathies; Congenital Heart Disease
614823: AD Aortic valve disease 2 617439: AD {Craniosynostosis 7, susceptibility to}
AD
TGFB2 190220 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies
614816: AD Loeys-Dietz syndrome 4 AD
TGFB3
190230
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Arrythmogenic Right Ventricular Cardiomyopathy; Aortopathies; Comprehensive Arrythmias
107970: AD Arrhythmogenic right ventricular dysplasia 1 615582: AD Loeys-Dietz syndrome 5
AD
TGFBR1
190181 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies
609192: AD Loeys-Dietz syndrome 1 132800: AD {Multiple self-healing squamous epithelioma, susceptibility to}
AD
TGFBR2
190182
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies
614331: Colorectal cancer, hereditary nonpolyposis, type 6 133239: Esophageal cancer, somatic 610168: AD Loeys-Dietz syndrome 2
AD
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
48 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
1. Abbreviations: Autosomal Dominant (AD); Autosomal Recession (AR); Isolated Cases (IC); Multifactorial (MF); Somatic Mutations (SM; Note: somatic mutations are not reported); XL (X-linked); XLD (X-linked Dominant); and XLR (X-linked Recessive).
2. ATP7A: The following ATP7A hg19 coordinates have been excluded from this assay: chrX:77269723-77269729, chrX:77278955- 77279156
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
49 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
CONGENITAL HEART DISEASE (CHD) PANEL
Congenital heart disease (CHD) is a common cause of neonatal morbidity and mortality. CHD can present in multifactorial and syndromic forms. CHD-associated genetic syndromes may occur in association with teratogens, chromosomal abnormalities, or single gene defects. A genetics evaluation is warranted in neonates who have congenital cardiac malformations associated with unusual physical features or other organ system malformations. Early molecular diagnosis of CHD-associated genetic syndromes is important as the genetic etiology may guide further diagnosis, management, and treatment. In addition, the presence of a syndrome in the family may warrant genetic counseling for the patient’s family.
The Congenital Heart Disease (CHD) Panel contains the following 43 genes.
Gene MIM Disease Category OMIM Phenotype Inheritance
ACTC1
102540
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction
612794: AD Atrial septal defect 5 613424: AD Cardiomyopathy, dilated, 1R 612098: AD Cardiomyopathy, hypertrophic, 11 613424: AD Left ventricular noncompaction 4
AD
ACVR2B 602730 Comprehensive Cardiovascular; Congenital Heart Disease
613751: Heterotaxy, visceral, 4, autosomal None
ALMS1 606844 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease
203800: AR Alstrom syndrome AR
BCOR 300485 Comprehensive Cardiovascular; Congenital Heart Disease
300166: XLD Microphthalmia, syndromic 2 XLD
BRAF
164757
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Noonan Spectrum Disorders
211980: Adenocarcinoma of lung, somatic 115150: AD Cardiofaciocutaneous syndrome Colorectal cancer, somatic (3) 613707: AD LEOPARD syndrome 3 Melanoma, malignant, somatic (3) Nonsmall cell lung cancer, somatic (3) 613706: AD Noonan syndrome 7
AD
CBL
165360
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Noonan Spectrum Disorders
607785: AD, SM ?Juvenile myelomonocytic leukemia 613563: AD Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia
AD, SM
CHD7
608892
Comprehensive Cardiovascular; Congenital Heart Disease
214800: AD CHARGE syndrome 612370: AD Hypogonadotropic hypogonadism 5 with or without anosmia
AD
CRELD1
607170
Comprehensive Cardiovascular; Congenital Heart Disease
606217: AD Atrioventricular septal defect, partial, with heterotaxy syndrome
606217: AD {Atrioventricular septal defect, susceptibility to, 2}
AD
DNAH5 603335 Comprehensive Cardiovascular; Congenital Heart Disease
608644: Ciliary dyskinesia, primary, 3, with or without situs inversus
None
ELN 130160 Comprehensive Cardiovascular; Congenital Heart Disease
123700: AD Cutis laxa, AD 185500: AD Supravalvar aortic stenosis
AD
FOXH1 603621 Comprehensive Cardiovascular; Congenital Heart Disease
None None
GATA4
600576
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease
607941: AD Atrial septal defect 2 614430: AD Atrioventricular septal defect 4 615542: AD ?Testicular anomalies with or without congenital heart disease
187500: AD Tetralogy of Fallot 614429: AD Ventricular septal defect 1
AD
GATA6
601656
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease
614475: AD Atrial septal defect 9 614474: AD Atrioventricular septal defect 5 600001: AD Pancreatic agenesis and congenital
AD
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
50 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
Gene MIM Disease Category OMIM Phenotype Inheritance
heart defects 217095: Persistent truncus arteriosus 187500: AD Tetralogy of Fallot
GDF1
602880
Comprehensive Cardiovascular; Congenital Heart Disease
613854: AD Congenital heart defects, multiple types, 6 208530: AR Right atrial isomerism (Ivemark)
AD, AR
GJA1
121014
Comprehensive Cardiovascular; Congenital Heart Disease
600309: AD Atrioventricular septal defect 3 218400: AR Craniometaphyseal dysplasia, AR 617525: AD Erythrokeratodermia variabilis et progressiva 3 241550: AR Hypoplastic left heart syndrome 1 164200: AD Oculodentodigital dysplasia 257850: AR Oculodentodigital dysplasia, AR 104100: AD Palmoplantar keratoderma with congenital alopecia 186100: AD Syndactyly, type III
AD, AR
GPC3
300037
Comprehensive Cardiovascular; Congenital Heart Disease
312870: XLR Simpson-Golabi-Behmel syndrome, type 1 194070: Wilms tumor, somatic
XLR
HAND1 602406 Comprehensive Cardiovascular; Congenital Heart Disease
None None
HRAS
190020
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Noonan Spectrum Disorders
109800: {Bladder cancer, somatic} 218040: AD, IC Congenital myopathy with excess of muscle spindles 218040: AD, IC Costello syndrome 162900: {Nevus sebaceous or woolly hair nevus, somatic} 163200: Schimmelpenning-Feuerstein-Mims
syndrome, somatic mosaic 137550: {Spitz nevus or nevus spilus, somatic} 188470: {Thyroid carcinoma, follicular, somatic}
AD, IC
JAG1
601920
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease
118450: AD Alagille syndrome 1 617992: ?Deafness, congenital heart defects, and posterior embryotoxon 187500: AD Tetralogy of Fallot
AD
KRAS
190070
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Noonan Spectrum Disorders
108010: Arteriovenous malformation of the brain, somatic 109800: Bladder cancer, somatic 114480: Breast cancer, somatic 615278: Cardiofaciocutaneous syndrome 2 137215: Gastric cancer, somatic 601626: AD Leukemia, acute myeloid 211980: Lung cancer, somatic 609942: AD Noonan syndrome 3 260350: Pancreatic carcinoma, somatic 614470: AD RAS-associated autoimmune leukoproliferative disorder 163200: Schimmelpenning-Feuerstein-Mims syndrome, somatic mosaic
AD
LEFTY2 601877 Comprehensive Cardiovascular; Congenital Heart Disease
None None
MAP2K1
176872
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Noonan Spectrum Disorders
615279: Cardiofaciocutaneous syndrome 3
None
MAP2K2
601263
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Noonan Spectrum Disorders
615280: Cardiofaciocutaneous syndrome 4
None
MED13L
608771
Comprehensive Cardiovascular; Congenital Heart Disease
616789: AD Mental retardation and distinctive facial features with or without cardiac defects 608808: AD Transposition of the great arteries, dextro-looped 1
AD
MEIS2 601740 Comprehensive Cardiovascular; Congenital Heart Disease
600987: AD Cleft palate, cardiac defects, and mental retardation
AD
MYH6 160710 Comprehensive Cardiovascular; Comprehensive 614089: Atrial septal defect 3 AD
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
51 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
Gene MIM Disease Category OMIM Phenotype Inheritance
Cardiomyopathy; Congenital Heart Disease; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy
613252: Cardiomyopathy, dilated, 1EE 613251: AD Cardiomyopathy, hypertrophic, 14 614090: {Sick sinus syndrome 3}
NKX2-5
600584
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Congenital Heart Disease
108900: AD Atrial septal defect 7, with or without AV conduction defects 217095: Conotruncal heart malformations, variable 614435: AD Hypoplastic left heart syndrome 2 225250: AD Hypothyroidism, congenital nongoitrous, 5 187500: AD Tetralogy of Fallot 614432: AD Ventricular septal defect 3
AD
NKX2-6 611770 Comprehensive Cardiovascular; Congenital Heart Disease
217095: Conotruncal heart malformations 217095: Persistent truncus arteriosus
None
NODAL 601265 Comprehensive Cardiovascular; Congenital Heart Disease
270100: AD Heterotaxy, visceral, 5 AD
NOTCH1
190198
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies; Congenital Heart Disease
616028: AD Adams-Oliver syndrome 5 109730: AD Aortic valve disease 1
AD
NR2F2 107773 Comprehensive Cardiovascular; Congenital Heart Disease
615779: AD Congenital heart defects, multiple types, 4
AD
NRAS
164790
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Noonan Spectrum Disorders
114500: Colorectal cancer, somatic 162900: Epidermal nevus, somatic 137550: Melanocytic nevus syndrome, congenital, somatic 249400: Neurocutaneous melanosis, somatic 613224: AD Noonan syndrome 6 614470: ?RAS-associated autoimmune lymphoproliferative syndrome type IV, somatic 163200: Schimmelpenning-Feuerstein-Mims syndrome, somatic mosaic 188470: Thyroid carcinoma, follicular, somatic
AD
NSD1 606681 Comprehensive Cardiovascular; Congenital Heart Disease
601626: AD Leukemia, acute myeloid 117550: AD Sotos syndrome 1
AD
PTPN11
176876
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Hypertrophic Cardiomyopathy; Noonan Spectrum Disorders
151100: AD LEOPARD syndrome 1 607785: Leukemia, juvenile myelomonocytic, somatic 156250: AD Metachondromatosis 163950: AD Noonan syndrome 1
AD
RAF1
164760
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Noonan Spectrum Disorders
615916: AD Cardiomyopathy, dilated, 1NN 611554: LEOPARD syndrome 2 611553: AD Noonan syndrome 5
AD
RIT1
609591
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Noonan Spectrum Disorders
615355: AD Noonan syndrome 8
AD
SHOC2
602775
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Noonan Spectrum Disorders
607721: AD Noonan-like syndrome with loose anagen hair
AD
SMAD6 602931 Comprehensive Cardiovascular; Aortopathies; Congenital Heart Disease
614823: AD Aortic valve disease 2 617439: AD {Craniosynostosis 7, susceptibility to}
AD
SOS1
182530
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Noonan Spectrum Disorders
135300: AD ?Fibromatosis, gingival, 1
610733: AD Noonan syndrome 4
AD
TBX1
602054
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease
217095: Conotruncal anomaly face syndrome 188400: AD DiGeorge syndrome
187500: AD Tetralogy of Fallot 192430: AD Velocardiofacial syndrome
AD
TBX5 601620 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease
142900: AD Holt-Oram syndrome AD
ZFPM2
603693
Comprehensive Cardiovascular; Congenital Heart Disease
610187: Diaphragmatic hernia 3 187500: AD Tetralogy of Fallot 616067: AD 46XY sex reversal 9
AD
ZIC3 300265 Comprehensive Cardiovascular; Congenital Heart Disease
306955: XLR Congenital heart defects, nonsyndromic, 1, XL
XLR, XL
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
52 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
Gene MIM Disease Category OMIM Phenotype Inheritance
306955: XLR Heterotaxy, visceral, 1, XL 314390: XLR VACTERL association, XL
1. Abbreviations: Autosomal Dominant (AD); Autosomal Recession (AR); Isolated Cases (IC); Multifactorial (MF); Somatic Mutations (SM;
Note: somatic mutations are not reported); XL (X-linked); XLD (X-linked Dominant); and XLR (X-linked Recessive). 2. GATA6: The following GATA6 hg19 coordinates have been excluded from this assay: chr18:19749269-19749275
3. LEFTY2: The following LEFTY2 hg19 coordinates have been excluded from this assay: chr1:226127049-226127311
4. TBX1: The following TBX1 hg19 coordinates have been excluded from this assay: chr22:19748416-19748814
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
53 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
FAMILIAL HYPERCHOLESTEROLEMIA (FH) PANEL
Familial hypercholesterolemia (FH) is characterized by elevated plasma levels of low-density lipoprotein (LDL) cholesterol from the time of birth. Commonly, mutations in genes encoding the LDL receptor, apolipoprotein B, and proprotein convertase subtilisin/kexin type 9 cause FH. These mutations are inherited in an autosomal dominant manner. In more rare cases, homozygous and compound heterozygosity FH as well as double heterozygosity have been reported. Typically, affected individuals may experience premature cardiovascular events, which may manifest as angina or myocardial infarction and can have an earlier onset in those with homozygous FH. External signs of hypercholesterolemia can also manifest in the form of xanthomata, which can occur around the eyelids and within the tendons of the elbows, hands, knees, and feet. Early diagnosis and treatment can reduce morbidity and mortality. The genetic status of at-risk family members can be clarified by molecular genetic testing, especially if the pathogenic variant has been identified in an affected family member, or by measurement of LDL cholesterol concentration.
The Familial Hypercholesterolemia (FH) Panel contains the following 4 genes.
Gene MIM Disease Category OMIM Phenotype Inheritance
APOB
107730
Comprehensive Cardiovascular; Familial Hypercholesterolemia
144010: AD Hypercholesterolemia, due to ligand-defective apo B 615558: AR Hypobetalipoproteinemia
AD, AR
LDLR 606945 Comprehensive Cardiovascular; Familial Hypercholesterolemia
143890: AD Hypercholesterolemia, familial 143890: AD LDL cholesterol level QTL2
AD
LDLRAP1 605747 Comprehensive Cardiovascular; Familial Hypercholesterolemia
603813: AR Hypercholesterolemia, familial, AR AR
PCSK9
607786 Comprehensive Cardiovascular; Familial Hypercholesterolemia
603776: Hypercholesterolemia, familial, 3
603776: {Low density lipoprotein cholesterol level QTL 1}
None
1. Abbreviations: Autosomal Dominant (AD); Autosomal Recession (AR); Isolated Cases (IC); Multifactorial (MF); Somatic Mutations (SM; Note: somatic mutations are not reported); XL (X-linked); XLD (X-linked Dominant); and XLR (X-linked Recessive).
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
54 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
PULMONARY HYPERTENSION (PAH) PANEL
Pulmonary arterial hypertension (PAH) is marked by obstruction of the small pulmonary arteries leading to an increase in resistance to blood flow through the lungs. The abnormally elevated pressure in the pulmonary circulation system can lead to progressive heart failure with initial symptoms including dyspnea, fatigue, syncope, chest pain, palpitations, and leg edema. PAH can be heritable in an autosomal dominant form with identical signs and symptoms to PAH of unknown etiology. In some inherited instances, pathogenic variants that disrupt the assembly of bone morphogenetic protein receptors tend to exhibit a more severe phenotype. Continuous intravenous epoprostenol is standard care for individuals with life-threatening PAH. A small minority of individuals respond well to long term oral calcium channel blockers.
The Pulmonary Hypertension Panel contains the following 10 genes.
Gene MIM Disease Category OMIM Phenotype Inheritance
ACVRL1
601284
Comprehensive Cardiovascular; Hereditary Hemorrhagic Telangiectasia; Pulmonary Hypertension
600376: AD Telangiectasia, hereditary hemorrhagic, type 2
AD
BMPR1B
603248
Comprehensive Cardiovascular; Pulmonary Hypertension
609441: AR Acromesomelic dysplasia, Demirhan type 616849: AD Brachydactyly, type A1, D 112600: AD Brachydactyly, type A2
AD, AR
BMPR2
600799
Comprehensive Cardiovascular; Pulmonary Hypertension
178600: AD Pulmonary hypertension, familial primary, 1, with or without HHT 178600: AD Pulmonary hypertension, primary, fenfluramine or dexfenfluramine-associated 265450: AD Pulmonary venoocclusive disease 1
AD
CAV1
601047
Comprehensive Cardiovascular; Pulmonary Hypertension
612526: ?Lipodystrophy, congenital generalized, type 3
606721: AD ?Partial lipodystrophy, congenital cataracts, and neurodegeneration syndrome 615343: AD Pulmonary hypertension, primary, 3
AD
EIF2AK4 609280 Comprehensive Cardiovascular; Pulmonary Hypertension
234810: AR Pulmonary venoocclusive disease 2
AR
ENG
131195
Comprehensive Cardiovascular; Hereditary
Hemorrhagic Telangiectasia; Pulmonary Hypertension
187300: AD Telangiectasia, hereditary hemorrhagic, type 1
AD
GDF2
605120
Comprehensive Cardiovascular; Hereditary Hemorrhagic Telangiectasia; Pulmonary Hypertension
615506: AD Telangiectasia, hereditary hemorrhagic, type 5
AD
KCNA5
176267
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Comprehensive Arrythmias; Pulmonary Hypertension
612240: AD Atrial fibrillation, familial, 7
AD
KCNK3 603220 Comprehensive Cardiovascular; Pulmonary Hypertension
615344: AD Pulmonary hypertension, primary, 4
AD
SMAD9 603295 Comprehensive Cardiovascular; Pulmonary Hypertension
615342: AD Pulmonary hypertension, primary, 2 AD
1. Abbreviations: Autosomal Dominant (AD); Autosomal Recession (AR); Isolated Cases (IC); Multifactorial (MF); Somatic Mutations (SM; Note: somatic mutations are not reported); XL (X-linked); XLD (X-linked Dominant); and XLR (X-linked Recessive).
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
55 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
METABOLIC CARDIOMYOPATHY PANEL
Cardiometabolic syndrome is a constellation of metabolic dysfunction disorders characterized by insulin resistance, impaired glucose tolerance, atherogenic dyslipidemia, hypertension, intra-abdominal adiposity, and an overall clustering of these cardiovascular risk factors. Current approaches to the treatment of cardiometabolic syndrome include control of cardiovascular risk factors with an emphasis on regaining the balance between energy intake and expenditure. The highly heterogeneous nature of cardiometabolic conditions and overlapping phenotypes can challenge clinical assessment. Therefore, targeted gene panels utilizing next-generation sequencing can prove to be effective in prioritizing diagnosis of cardiometabolic conditions and may help distinguish patients who require further investigation.
The Metabolic Cardiomyopathy Panel contains the following 24 genes.
Gene MIM Disease Category OMIM Phenotype Inheritance
ACADVL
609575
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Metabolic Cardiomyopathy
201475: AR VLCAD deficiency
AR
AGL
610860 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Hypertrophic Cardiomyopathy; Metabolic Cardiomyopathy
232400: AR Glycogen storage disease IIIa 232400: AR Glycogen storage disease IIIb
AR
ALG1
605907
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Metabolic Cardiomyopathy
608540: AR Congenital disorder of glycosylation, type Ik
AR
ALG12
607144 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Metabolic Cardiomyopathy
607143: AR Congenital disorder of glycosylation, type Ig
AR
ARSB
611542
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Metabolic Cardiomyopathy
253200: AR Mucopolysaccharidosis type VI (Maroteaux-Lamy)
AR
CPT2
600650
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Hypertrophic Cardiomyopathy; Metabolic Cardiomyopathy
600649: AR CPT II deficiency, infantile 608836: AR CPT II deficiency, lethal neonatal 255110: AR, AD CPT II deficiency, myopathic, stress-induced 614212: AR, AD {Encephalopathy, acute, infection-induced, 4, susceptibility to}
AD, AR
DOLK
610746
Comprehensive Cardiovascular;
Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Metabolic Cardiomyopathy
610768: AR Congenital disorder of glycosylation, type Im
AR
FKRP
606596
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Metabolic Cardiomyopathy
613153: AR Muscular dystrophy- dystroglycanopathy (congenital with brain and eye anomalies), type A, 5 606612: AR Muscular dystrophy- dystroglycanopathy (congenital with or without mental retardation), type B, 5
607155: AR Muscular dystrophy- dystroglycanopathy (limb-girdle), type C, 5
AR
GAA
606800 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Hypertrophic Cardiomyopathy; Metabolic Cardiomyopathy
232300: AR Glycogen storage disease II
AR
GBA
606463
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Metabolic Cardiomyopathy
608013: AR Gaucher disease, perinatal lethal 230800: AR Gaucher disease, type I
230900: AR Gaucher disease, type II 231000: AR Gaucher disease, type III 231005: AR Gaucher disease, type IIIC 127750: AD {Lewy body dementia, susceptibility to} 168600: IC, MF {Parkinson disease, late-onset, susceptibility to}
AD, AR, IC,
MF
GBE1
607839
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Metabolic Cardiomyopathy
232500: AR Glycogen storage disease IV 263570: AR Polyglucosan body disease, adult form
AR
GLA
300644 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Hypertrophic Cardiomyopathy; Metabolic Cardiomyopathy
301500: XL Fabry disease 301500: XL Fabry disease, cardiac variant
XL
GLB1 611458 Comprehensive Cardiovascular; 230500: AR GM1-gangliosidosis, type I AR
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
56 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
Gene MIM Disease Category OMIM Phenotype Inheritance
Comprehensive Cardiomyopathy; Metabolic Cardiomyopathy
230600: AR GM1-gangliosidosis, type II 230650: AR GM1-gangliosidosis, type III 253010: AR Mucopolysaccharidosis type IVB (Morquio)
GUSB
611499
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Metabolic Cardiomyopathy
253220: AR Mucopolysaccharidosis VII
AR
HADHA
600890
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Metabolic Cardiomyopathy
609016: AR Fatty liver, acute, of pregnancy 609016: AR HELLP syndrome, maternal, of pregnancy 609016: AR LCHAD deficiency 609015: AR Trifunctional protein deficiency
AR
HEXB
606873
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Metabolic Cardiomyopathy
268800: AR Sandhoff disease, infantile, juvenile, and adult forms
AR
IDUA
252800 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Metabolic Cardiomyopathy
607014: AR Mucopolysaccharidosis Ih 607015: AR Mucopolysaccharidosis Ih/s 607016: AR Mucopolysaccharidosis Is
AR
LAMP2
309060
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Left Ventricular Ncompaction; Metabolic Cardiomyopathy
300257: XLD Danon disease
XLD
MTO1
614667
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Metabolic Cardiomyopathy
614702: AR Combined oxidative phosphorylation deficiency 10
AR
PCCA
232000 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Metabolic Cardiomyopathy
606054: AR Propionicacidemia
AR
PCCB
232050
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Metabolic Cardiomyopathy
606054: AR Propionicacidemia
AR
SLC22A5
603377
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Metabolic Cardiomyopathy
212140: AR Carnitine deficiency, systemic primary
AR
SLC25A20
613698 Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Metabolic Cardiomyopathy
212138: AR Carnitine-acylcarnitine translocase deficiency
AR
TAZ
300394
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Dilated Cardiomyopathy; Left Ventricular Ncompaction; Metabolic Cardiomyopathy
302060: XLR Barth syndrome
XLR
1. Abbreviations: Autosomal Dominant (AD); Autosomal Recession (AR); Isolated Cases (IC); Multifactorial (MF); Somatic Mutations (SM;
Note: somatic mutations are not reported); XL (X-linked); XLD (X-linked Dominant); and XLR (X-linked Recessive).
2. GBA: The following GBA hg19 coordinates have been excluded from this assay: chr1:155207120-155207380, chr1:155204774-
155204902, chr1:155208296-155208452
3. LAMP2: The following LAMP2 hg19 coordinates have been excluded from this assay: chrX:119604075-119604081
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
57 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
NOONAN SPECTRUM DISORDERS PANEL
Noonan Spectrum Disorders (NSD), or RASopathies, are genetically heterogeneous developmental syndromes caused by heterozygous germline mutations in genes involved in the Ras/MAPK signaling pathway. This pathway is essential for regulation of the cell cycle, cell differentiation, and cellular growth. Noonan Spectrum Disorders occur in 1 in 1,000 to 1 in 2,500 live births. Performing postnatal genetic testing can be clinically useful for individuals that display characteristic features (cardiac abnormalities, specific facial dysmorphisms, developmental delay/intellectual disability, etc.), or prenatally for fetuses that present with certain ultrasound findings (cystic hygroma, increased nuchal translucency, etc.) after a normal chromosome analysis.
The Noonan Spectrum Disorders Panel contains the following 18 genes.
Gene MIM Disease Category OMIM Phenotype Inheritance
BRAF
164757
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Noonan Spectrum Disorders
211980: Adenocarcinoma of lung, somatic 115150: AD Cardiofaciocutaneous syndrome Colorectal cancer, somatic (3) 613707: AD LEOPARD syndrome 3 Melanoma, malignant, somatic (3) Nonsmall cell lung cancer, somatic (3) 613706: AD Noonan syndrome 7
AD
CBL
165360
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Noonan Spectrum Disorders
607785: AD, SM ?Juvenile myelomonocytic leukemia 613563: AD Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia
AD, SM
HRAS
190020
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Noonan Spectrum Disorders
109800: {Bladder cancer, somatic} 218040: AD, IC Congenital myopathy with excess of muscle spindles 218040: AD, IC Costello syndrome 162900: {Nevus sebaceous or woolly hair nevus, somatic} 163200: Schimmelpenning-Feuerstein-Mims syndrome, somatic mosaic
137550: {Spitz nevus or nevus spilus, somatic} 188470: {Thyroid carcinoma, follicular, somatic}
AD, IC
KRAS
190070
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Noonan Spectrum Disorders
108010: Arteriovenous malformation of the brain, somatic 109800: Bladder cancer, somatic 114480: Breast cancer, somatic 615278: Cardiofaciocutaneous syndrome 2 137215: Gastric cancer, somatic 601626: AD Leukemia, acute myeloid 211980: Lung cancer, somatic 609942: AD Noonan syndrome 3 260350: Pancreatic carcinoma, somatic 614470: AD RAS-associated autoimmune leukoproliferative disorder 163200: Schimmelpenning-Feuerstein-Mims syndrome, somatic mosaic
AD
LZTR1 600574 Noonan Spectrum Disorders 616564: AD Noonan syndrome 10 615670: AD {Schwannomatosis-2, susceptibility to}
AD
MAP2K1
176872
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Noonan Spectrum Disorders
615279: Cardiofaciocutaneous syndrome 3
None
MAP2K2
601263
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Noonan Spectrum Disorders
615280: Cardiofaciocutaneous syndrome 4
None
NF1
613113
Noonan Spectrum Disorders
607785: AD, SM Leukemia, juvenile myelomonocytic
162210: AD Neurofibromatosis, familial spinal 162200: AD Neurofibromatosis, type 1
AD, SM
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
58 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
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Gene MIM Disease Category OMIM Phenotype Inheritance
601321: AD Neurofibromatosis-Noonan syndrome 193520: AD Watson syndrome
NRAS
164790
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Noonan Spectrum Disorders
114500: Colorectal cancer, somatic 162900: Epidermal nevus, somatic 137550: Melanocytic nevus syndrome, congenital, somatic 249400: Neurocutaneous melanosis, somatic 613224: AD Noonan syndrome 6 614470: ?RAS-associated autoimmune lymphoproliferative syndrome type IV, somatic 163200: Schimmelpenning-Feuerstein-Mims syndrome, somatic mosaic 188470: Thyroid carcinoma, follicular, somatic
AD
PPP1CB 600590 Noonan Spectrum Disorders 617506: AD Noonan syndrome-like disorder with loose anagen hair 2
AD
PTPN11
176876
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Hypertrophic Cardiomyopathy; Noonan Spectrum Disorders
151100: AD LEOPARD syndrome 1 607785: Leukemia, juvenile myelomonocytic, somatic
156250: AD Metachondromatosis 163950: AD Noonan syndrome 1
AD
RAF1
164760
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy; Noonan Spectrum Disorders
615916: AD Cardiomyopathy, dilated, 1NN 611554: LEOPARD syndrome 2 611553: AD Noonan syndrome 5
AD
RASA2 601589 Noonan Spectrum Disorders None None
RIT1
609591
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Noonan Spectrum Disorders
615355: AD Noonan syndrome 8
AD
SHOC2
602775
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Noonan Spectrum Disorders
607721: AD Noonan-like syndrome with loose anagen hair
AD
SOS1
182530
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Congenital Heart Disease; Noonan Spectrum Disorders
135300: AD ?Fibromatosis, gingival, 1 610733: AD Noonan syndrome 4
AD
SOS2 601247 Noonan Spectrum Disorders 616559: AD Noonan syndrome 9 AD
SPRED1 609291 Noonan Spectrum Disorders 611431: AD Legius syndrome AD
6. Abbreviations: Autosomal Dominant (AD); Autosomal Recession (AR); Isolated Cases (IC); Multifactorial (MF); Somatic Mutations (SM; Note: somatic mutations are not reported); XL (X-linked); XLD (X-linked Dominant); and XLR (X-linked Recessive).
7. RASA2: The following RASA2 hg19 coordinates have been excluded from this assay: chr3:141235158-141235284.
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
59 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
HEREDITARY HEMORRHAGIC TELANGIECTASIA PANEL
This group comprises genes with cardiac-related disease involvement that cannot be readily classified in the preceding groups that is often part of a constellation of findings associated with syndromic features.
The Hereditary Hemorrhagic Telangiectasia Panel contains the following 5 genes.
Gene MIM Disease Category OMIM Phenotype Inheritance
ACVRL1
601284
Comprehensive Cardiovascular; Hereditary Hemorrhagic Telangiectasia; Pulmonary
Hypertension
600376: AD Telangiectasia, hereditary hemorrhagic, type 2
AD
ENG
131195 Comprehensive Cardiovascular; Hereditary
Hemorrhagic Telangiectasia; Pulmonary Hypertension
187300: AD Telangiectasia, hereditary hemorrhagic, type 1
AD
GDF2
605120
Comprehensive Cardiovascular; Hereditary Hemorrhagic Telangiectasia; Pulmonary
Hypertension
615506: AD Telangiectasia, hereditary hemorrhagic, type 5
AD
RASA1
139150
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Hereditary
Hemorrhagic Telangiectasia
605462: Basal cell carcinoma, somatic 608354: AD Capillary malformation-
arteriovenous malformation 608355: AD Parkes Weber syndrome
AD
SMAD4
600993
Comprehensive Cardiovascular; Comprehensive Cardiomyopathy; Aortopathies;
Hereditary Hemorrhagic Telangiectasia
175050: AD Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome
139210: AD Myhre syndrome 260350: Pancreatic cancer, somatic
174900: AD Polyposis, juvenile intestinal
AD
1. Abbreviations: Autosomal Dominant (AD); Autosomal Recession (AR); Isolated Cases (IC); Multifactorial (MF); Somatic Mutations (SM; Note: somatic mutations are not reported); XL (X-linked); XLD (X-linked Dominant); and XLR (X-linked Recessive).
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
New York, NY 10029
60 CLIA #: 33D2097541 T: 800-298-6470 F: 212-241-0139
www.sema4.com
References
General References:
1. Pua JC, et al. Development of a Comprehensive Sequencing Assay for Inherited Cardiac Condition Genes. J Cardiovasc Transl Res. 2016 Feb;9(1):3-11. 2. Cirino AL, et al. Role of Genetic Testing in Inherited Cardiovascular Disease: A Review. JAMA Cardiol. 2017 Oct 1;2(10):1153-1160. 3. Mital S, et al. Enhancing Literacy in Cardiovascular Genetics: A Scientific Statement From the American Heart Association. Circ Cardiovasc Genet. 2016 Oct;9(5):448-467. 4. Nadar SK and Sandhu K. Genes and Cardiovascular Disease: Where do we go from here? Sultan Qaboos Univ Med J. 2015 Nov;15(4):e448-51. 5. Kathiresan S and Srivastava D. Genetics of human cardiovascular disease. Cell. 2012 Mar 16;148(6):1242-57. 6. Celestino-Soper PB, et al. Validation and Utilization of a Clinical Next-Generation Sequencing Panel for Selected Cardiovascular Disorders. Front Cardiovasc Med. 2017 Mar 15;4:11.
http://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds) 7. Lee KA, Williams B, Roza K, Ferguson H, David K, Eddleman K, Stone J, Edelmann L, Richard G, Gelb BD, Kornreich R. PTPN11 analysis for the prenatal diagnosis of Noonan syndrome
in fetuses with abnormal ultrasound findings. Clin Genet. 2009 Feb;75(2):190-4. doi: 10.1111/j.1399-0004.2008.01085.x. Epub 2008 Aug 26. PMID: 18759865 8. Croonen EA, Nillesen WM, Stuurman KE, Oudesluijs G, van de Laar IM, Martens L, Ockeloen C, Mathijssen IB, Schepens M, Ruiterkamp-Versteeg M, Scheffer H, Faas BH, van der
Burgt I, Yntema HG. Prenatal diagnostic testing of the Noonan syndrome genes in fetuses with abnormal ultrasound findings. Eu r J Hum Genet. 2013 Sep;21(9):936-42. doi: 10.1038/ejhg.2012.285. Epub 2013 Jan 16. PMID: 23321623
Gene-Specific References:
1. Abbott GW, Sesti F, Splawski I, Buck ME, Lehmann MH, Timothy KW, Keating MT,Goldstein SA. MiRP1 forms IKr potassium channels with HERG and is associated withcardiac arrhythmia. Cell. 1999 Apr 16;97(2):175-87. PubMed PMID: 10219239.
2. Abifadel M, Varret M, Rabès JP, Allard D, Ouguerram K, Devillers M, Cruaud C, Benjannet S, Wickham L, Erlich D, Derré A, Villéger L, Farnier M, Beucl er I,Bruckert E, Chambaz J, Chanu B, Lecerf JM, Luc G, Moulin P, Weissenbach J, PratA, Krempf M, Junien C, Seidah NG, Boileau C. Mutations in PCSK9 cause autosomaldominant hypercholesterolemia. Nat Genet. 2003 Jun;34(2):154-6. PubMed PMID:12730697.
3. Adegbola A, Musante L, Callewaert B, Maciel P, Hu H, Isidor B, Picker-Minh S, Le Caignec C, Delle Chiaie B, Vanakker O, Menten B, Dheedene A, Bockaert N,Roelens F, Decaestecker K, Silva J, Soares G, Lopes F, Najmabadi H, Kahrizi K,Cox GF, Angus SP, Staropoli JF, Fischer U, Suckow V, Bartsch O, Chess A, RopersHH, Wienker TF, Hübner C, Kaindl AM, Kalscheuer VM. Redefining the MED13Lsyndrome. Eur J Hum Genet. 2015 Oct;23(10):1308-17. doi: 10.1038/ejhg.2015.26.Epub 2015 Mar 11. PubMed PMID: 25758992; PubMed Central PMCID: PMC4592099.
4. Aharon-Peretz J, Rosenbaum H, Gershoni-Baruch R. Mutations in theglucocerebrosidase gene and Parkinson's disease in Ashkenazi Jews. N Engl J Med. 2004 Nov 4;351(19):1972- 7. PubMed PMID: 15525722.
5. Al Turki S, Manickaraj AK, Mercer CL, Gerety SS, Hitz MP, Lindsay S,D'Alessandro LC, Swaminathan GJ, Bentham J, Arndt AK, Louw J, Breckpot J,Gewillig M, Thienpont B, Abdul- Khaliq H, Harnack C, Hoff K, Kramer HH, SchubertS, Siebert R, Toka O, Cosgrove C, Watkins H, Lucassen AM, O'Kelly IM, Salmon AP, Bu'lock FA, Granados-Riveron J, Setchfield K, Thornborough C, Brook JD, Mulder B,Klaassen S, Bhattacharya S, Devriendt K, Fitzpatrick DF; UK10K Consortium, WilsonDI, Mital S, Hurles ME. Rare variants in NR2F2 cause congenital heart defects in humans. Am J Hum Genet. 2014 Apr 3;94(4):574-85. doi: 10.1016/j.ajhg.2014.03.007.Erratum in: Am J Hum Genet. 2016 Mar 3;98(3):592. Low, Jacoba [corrected to Louw,Jacoba]. Am J Hum Genet. 2014 Jul 3;95(1):126. PubMed PMID: 24702954; PubMedCentral PMCID: PMC3980509.
6. Aldahmesh MA, Khan AO, Mohamed JY, Alghamdi MH, Alkuraya FS. Identification ofa truncation mutation of acylglycerol kinase (AGK) gene in a novel autosomalrecessive cataract locus. Hum Mutat. 2012 Jun;33(6):960-2. doi:10.1002/humu.22071. Epub 2012 Apr 16. PubMed PMID: 22415731.
7. Almomani R, Verhagen JM, Herkert JC, Brosens E, van Spaendonck-Zwarts KY,Asimaki A, van der Zwaag PA, Frohn-Mulder IM, Bertoli-Avella AM, Boven LG, vanSlegtenhorst MA, van der Smagt JJ, van IJcken WF, Timmer B, van Stuijvenberg M,Verdijk RM, Saffitz JE, du Plessis FA, Michels M, Hofstra RM, Sinke RJ, vanTintelen JP, Wessels MW, Jongbloed JD, van de Laar IM. Biallelic TruncatingMutations in ALPK3 Cause Severe Pediatric Cardiomyopathy. J Am Coll Cardiol. 2016Feb 9;67(5):515-25. doi: 10.1016/j.jacc.2015.10.093. PubMed PMID: 26846950.
8. Anderson SL, Chung WK, Frezzo J, Papp JC, Ekstein J, DiMauro S, Rubin BY. Anovel mutation in NDUFS4 causes Leigh syndrome in an Ashkenazi Jewish family. JInherit Metab Dis. 2008 Dec;31 Suppl 2:S461-7. doi: 10.1007/s10545-008-1049-9.Epub 2008 Dec 26. PubMed PMID: 19107570.
9. Andresen BS, Bross P, Vianey-Saban C, Divry P, Zabot MT, Roe CR, Nada MA,Byskov A, Kruse TA, Neve S, Kristiansen K, Knudsen I, Corydon MJ, Gregersen N.Cloning and characterization of human very-long-chain acyl-CoA dehydrogenasecDNA, chromosomal assignment of the gene and identification in four patients ofnine different mutations within the VLCAD gene. Hum Mol Genet. 1996Apr;5(4):461-72. Erratum in: Hum Mol Genet 1996 Sep;5(9):1390. PubMed PMID:8845838.
10. Antonicka H, Leary SC, Guercin GH, Agar JN, Horvath R, Kennaway NG, HardingCO, Jaksch M, Shoubridge EA. Mutations in COX10 result in a defect inmitochondrial heme A biosynthesis and account for multiple, early-onset clinical phenotypes associated with isolated COX deficiency. Hum Mol Genet. 2003 Oct15;12(20):2693-702. Epub 2003 Aug 19. PubMed PMID: 12928484.
11. Antonicka H, Mattman A, Carlson CG, Glerum DM, Hoffbuhr KC, Leary SC, KennawayNG, Shoubridge EA. Mutations in COX15 produce a defect in the mitochondrial heme biosynthetic pathway, causing early-onset fatal hypertrophic cardiomyopathy. Am JHum Genet. 2003 Jan;72(1):101-14. Epub 2002 Dec 9. PubMed PMID: 12474143; PubMed Central PMCID: PMC378614.
12. Antzelevitch C, Pollevick GD, Cordeiro JM, Casis O, Sanguinetti MC, Aizawa Y, Guerchicoff A, Pfeiffer R, Oliva A, Wollnik B, Gelber P, Bonaros EP Jr,Burashnikov E, Wu Y, Sargent JD, Schickel S, Oberheiden R, Bhatia A, Hsu LF,Haïssaguerre M, Schimpf R, Borggrefe M, Wolpert C. Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized byST-segment elevation, short QT intervals, and sudden cardiac death. Circulation. 2007 Jan 30;115(4):442-9. Epub 2007 Jan 15. PubMed PMID: 17224476; PubMed CentralPMCID: PMC1952683.
13. Aoki Y, Niihori T, Banjo T, Okamoto N, Mizuno S, Kurosawa K, Ogata T, TakadaF, Yano M, Ando T, Hoshika T, Barnett C, Ohashi H, Kawame H, Hasegawa T, Okutani T, Nagashima T, Hasegawa S, Funayama R, Nagashima T, Nakayama K, Inoue S,Watanabe Y, Ogura T, Matsubara Y. Gain-of-function mutations in RIT1 cause Noonan syndrome, a RAS/MAPK pathway syndrome. Am J Hum Genet. 2013 Jul 11;93(1):173-80. doi: 10.1016/j.ajhg.2013.05.021. Epub 2013 Jun 20. PubMed PMID: 23791108; PubMed Central PMCID: PMC3710767.
14. Aoki Y, Niihori T, Banjo T, Okamoto N, Mizuno S, Kurosawa K, Ogata T, TakadaF, Yano M, Ando T, Hoshika T, Barnett C, Ohashi H, Kawame H, Hasegawa T, Okutani T, Nagashima T, Hasegawa S, Funayama R, Nagashima T, Nakayama K, Inoue S,Watanabe Y, Ogura T, Matsubara Y. Gain-of-function mutations in RIT1 cause Noonansyndrome, a RAS/MAPK pathway syndrome. Am J Hum Genet. 2013 Jul 11;93(1):173-80. doi: 10.1016/j.ajhg.2013.05.021. Epub 2013 Jun 20. PubMed PMID: 23791108; PubMed Central PMCID: PMC3710767.
15. Arndt AK, Schafer S, Drenckhahn JD, Sabeh MK, Plovie ER, Caliebe A, KlopockiE, Musso G, Werdich AA, Kalwa H, Heinig M, Padera RF, Wassilew K, Bluhm J,Harnack C, Martitz J, Barton PJ, Greutmann M, Berger F, Hubner N, Siebert R,Kramer HH, Cook SA, MacRae CA, Klaassen S. Fine mapping of the 1p36 deletionsyndrome identifies mutation of PRDM16 as a cause of cardiomyopathy. Am J HumGenet. 2013 Jul 11;93(1):67-77. doi: 10.1016/j.ajhg.2013.05.015. Epub 2013 Jun13. PubMed PMID: 23768516; PubMed Central PMCID: PMC3710750.
16. Awad MM, Dalal D, Cho E, Amat-Alarcon N, James C, Tichnell C, Tucker A,Russell SD, Bluemke DA, Dietz HC, Calkins H, Judge DP. DSG2 mutations contribute to arrhythmogenic right ventricular dysplasia/cardiomyopathy. Am J Hum Genet.2006 Jul;79(1):136-42. Epub 2006 Apr 28. PubMed PMID: 16773573; PubMed CentralPMCID: PMC1474134.
17. Bagnall RD, Yeates L, Semsarian C. Analysis of the Z-disc genes PDLIM3 andMYPN in patients with hypertrophic cardiomyopathy. Int J Cardiol. 2010 Dec3;145(3):601-2. doi: 10.1016/j.ijcard.2010.08.004. PubMed PMID: 20801532.
18. Bao Y, Kishnani P, Wu JY, Chen YT. Hepatic and neuromuscular forms of glycogenstorage disease type IV caused by mutations in the same glycogen-branching enzymegene. J Clin Invest. 1996 Feb 15;97(4):941-8. PubMed PMID: 8613547; PubMedCentral PMCID: PMC507139.
19. Barbier M, Gross MS, Aubart M, Hanna N, Kessler K, Guo DC, Tosolini L,Ho-Tin-Noe B, Regalado E, Varret M, Abifadel M, Milleron O, Odent S, Dupuis-GirodS, Faivre L, Edouard T, Dulac Y, Busa T, Gouya L, Milewicz DM, Jondeau G, BoileauC. MFAP5 loss-of-function mutations underscore the involvement of matrixalteration in the pathogenesis of familial thoracic aortic aneurysms anddissections. Am J Hum Genet. 2014 Dec 4;95(6):736-43. doi:10.1016/j.ajhg.2014.10.018. Epub 2014 Nov 26. PubMed PMID: 25434006; PubMedCentral PMCID: PMC4259978.
20. Barghuti F, Elian K, Gomori JM, Shaag A, Edvardson S, Saada A, Elpeleg O. The unique neuroradiology of complex I deficiency due to NDUFA12L defect. Mol GenetMetab. 2008 May;94(1):78-82. doi: 10.1016/j.ymgme.2007.11.013. Epub 2008 Jan 3.PubMed PMID: 18180188.
21. Baruffini E, Dallabona C, Invernizzi F, Yarham JW, Melchionda L, Blakely EL,Lamantea E, Donnini C, Santra S, Vijayaraghavan S, Roper HP, Burlina A, KopajtichR, Walther A, Strom TM, Haack TB, Prokisch H, Taylor RW, Ferrero I, Zeviani M,Ghezzi D. MTO1 mutations are associated with hypertrophic cardiomyopathy andlactic acidosis and cause respiratory chain deficiency in humans and yeast. HumMutat. 2013 Nov;34(11):1501-9. doi: 10.1002/humu.22393. Epub 2013 Sep 17. PubMed PMID: 23929671; PubMed Central PMCID: PMC4028987.
22. Baskin B, Skinner JR, Sanatani S, Terespolsky D, Krahn AD, Ray PN, Scherer SW,Hamilton RM. TMEM43 mutations associated with arrhythmogenic right ventricularcardiomyopathy in non-Newfoundland populations. Hum Genet. 2013Nov;132(11):1245-52. doi: 10.1007/s00439-013-1323-2. Epub 2013 Jun 29. PubMedPMID: 23812740.
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23. Baumann M, Giunta C, Krabichler B, Rüschendorf F, Zoppi N, Colombi M, Bittner RE, Quijano-Roy S, Muntoni F, Cirak S, Schreiber G, Zou Y, Hu Y, Romero NB,Carlier RY, Amberger A, Deutschmann A, Straub V, Rohrbach M, Steinmann B, RostásyK, Karall D, Bönnemann CG, Zschocke J, Fauth C. Mutations in FKBP14 cause avariant of Ehlers-Danlos syndrome with progressive kyphoscoliosis, myopathy, and hearing loss. Am J Hum Genet. 2012 Feb 10;90(2):201-16. doi:10.1016/j.ajhg.2011.12.004. Epub 2012 Jan 19. PubMed PMID: 22265013; PubMedCentral PMCID: PMC3276673.
24. Beffagna G, Occhi G, Nava A, Vitiello L, Ditadi A, Basso C, Bauce B, CarraroG, Thiene G, Towbin JA, Danieli GA, Rampazzo A. Regulatory mutations intransforming growth factor- beta3 gene cause arrhythmogenic right ventricularcardiomyopathy type 1. Cardiovasc Res. 2005 Feb 1;65(2):366-73. PubMed PMID:15639475.
25. Beltran-Valero de Bernabé D, Voit T, Longman C, Steinbrecher A, Straub V, YuvaY, Herrmann R, Sperner J, Korenke C, Diesen C, Dobyns W B, Brunner HG, vanBokhoven H, Brockington M, Muntoni F. Mutations in the FKRP gene can causemuscle-eye-brain disease and Walker-Warburg syndrome. J Med Genet. 2004May;41(5):e61. PubMed PMID: 15121789; PubMed Central PMCID: PMC1735772.
26. Berry V, Francis P, Reddy MA, Collyer D, Vithana E, MacKay I, Dawson G, Carey AH, Moore A, Bhattacharya SS, Quinlan RA. Alpha-B crystallin gene (CRYAB)mutation causes dominant congenital posterior polar cataract in humans. Am J Hum Genet. 2001 Nov;69(5):1141-5. Epub 2001 Sep 27. PubMed PMID: 11577372; PubMedCentral PMCID: PMC1274358.
27. Best DH, Sumner KL, Austin ED, Chung WK, Brown LM, Borczuk AC, Rosenzweig EB, Bayrak-Toydemir P, Mao R, Cahill BC, Tazelaar HD, Leslie KO, Hemnes AR, RobbinsIM, Elliott CG. EIF2AK4 mutations in pulmonary capillary hemangiomatosis. Chest. 2014 Feb;145(2):231-236. doi: 10.1378/chest.13-2366. PubMed PMID: 24135949;PubMed Central PMCID: PMC3921094.
28. Betz RC, Schoser BG, Kasper D, Ricker K, Ramírez A, Stein V, Torbergsen T, LeeYA, Nöthen MM, Wienker TF, Malin JP, Propping P, Reis A, Mortier W, Jentsch TJ,Vorgerd M, Kubisch C. Mutations in CAV3 cause mechanical hyperirritability ofskeletal muscle in rippling muscle disease. Nat Genet. 2001 Jul;28(3):218-9.PubMed PMID: 11431690.
29. Bienengraeber M, Olson TM, Selivanov VA, Kathmann EC, O'Cochlain F, Gao F,Karger AB, Ballew JD, Hodgson DM, Zingman LV, Pang YP, Alekseev AE, Terzic A.ABCC9 mutations identified in human dilated cardiomyopathy disrupt catalytic KATPchannel gating. Nat Genet. 2004 Apr;36(4):382-7. Epub 2004 Mar 21. PubMed PMID:15034580; PubMed Central PMCID: PMC1995438.
30. Bione S, D'Adamo P, Maestrini E, Gedeon AK, Bolhuis PA, Toniolo D. A novelX-linked gene, G4.5. is responsible for Barth syndrome. Nat Genet. 1996Apr;12(4):385-9. PubMed PMID: 8630491.
31. Bione S, Maestrini E, Rivella S, Mancini M, Regis S, Romeo G, Toniolo D.Identification of a novel X-linked gene responsible for Emery-Dreifuss musculardystrophy. Nat Genet. 1994 Dec;8(4):323-7. PubMed PMID: 7894480.
32. Boileau C, Guo DC, Hanna N, Regalado ES, Detaint D, Gong L, Varret M, Prakash SK, Li AH, d'Indy H, Braverman AC, Grandchamp B, Kwartler CS, Gouya L,Santos-Cortez RL, Abifadel M, Leal SM, Muti C, Shendure J, Gross MS, Rieder MJ,Vahanian A, Nickerson DA, Michel JB; National Heart, Lung, and Blood Institute(NHLBI) Go Exome Sequencing Project, Jondeau G, Milewicz DM. TGFB2 mutationscause familial thoracic aortic aneurysms and dissections associated with mild systemic features of Marfan syndrome. Nat Genet. 2012 Jul 8;44(8):916-21. doi:10.1038/ng.2348. PubMed PMID: 22772371; PubMed Central PMCID: PMC4033668.
33. Bonne G, Carrier L, Bercovici J, Cruaud C, Richard P, Hainque B, Gautel M,Labeit S, James M, Beckmann J, Weissenbach J, Vosberg HP, Fiszman M, Komajda M,Schwartz K. Cardiac myosin binding protein-C gene splice acceptor site mutationis associated with familial hypertrophic cardiomyopathy. Nat Genet. 1995Dec;11(4):438-40. PubMed PMID: 7493026.
34. Bonne G, Di Barletta MR, Varnous S, Bécane HM, Hammouda EH, Merlini L, MuntoniF, Greenberg CR, Gary F, Urtizberea JA, Duboc D, Fardeau M, Toniolo D, SchwartzK. Mutations in the gene encoding lamin A/C cause autosomal dominantEmery-Dreifuss muscular dystrophy. Nat Genet. 1999 Mar;21(3):285-8. PubMed PMID: 10080180.
35. Borozdin W, Bravo-Ferrer Acosta AM, Seemanova E, Leipoldt M, Bamshad MJ, UngerS, Kohlhase J. Contiguous hemizygous deletion of TBX5, TBX3, and RBM19 resulting in a combined phenotype of Holt-Oram and ulnar-mammary syndromes. Am J Med Genet A. 2006 Sep 1;140A(17):1880-6. PubMed PMID: 16892408.
36. Brauch KM, Karst ML, Herron KJ, de Andrade M, Pellikka PA, Rodeheffer RJ,Michels VV, Olson TM. Mutations in ribonucleic acid binding protein gene causefamilial dilated cardiomyopathy. J Am Coll Cardiol. 2009 Sep 1;54(10):930-41.doi: 10.1016/j.jacc.2009.05.038. PubMed PMID: 19712804; PubMed Central PMCID:PMC2782634.
37. Brems H, Chmara M, Sahbatou M, Denayer E, Taniguchi K, Kato R, Somers R,Messiaen L, De Schepper S, Fryns JP, Cools J, Marynen P, Thomas G, Yoshimura A,Legius E. Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis1-like phenotype. Nat Genet. 2007 Sep;39(9):1120-6. Epub 2007 Aug 19. PubMedPMID: 17704776.
38. Brockington M, Blake DJ, Prandini P, Brown SC, Torelli S, Benson MA, PontingCP, Estournet B, Romero NB, Mercuri E, Voit T, Sewry CA, Guicheney P, Muntoni F. Mutations in the fukutin-related protein gene (FKRP) cause a form of congenitalmuscular dystrophy with secondary laminin alpha2 deficiency and abnormalglycosylation of alpha-dystroglycan. Am J Hum Genet. 2001 Dec;69(6):1198-209.Epub 2001 Oct 8. PubMed PMID: 11592034; PubMed Central PMCID: PMC1235559.
39. Burashnikov E, Pfeiffer R, Barajas-Martinez H, Delpón E, Hu D, Desai M,Borggrefe M, Häissaguerre M, Kanter R, Pollevick GD, Guerchicoff A, Laiño R,Marieb M, Nademanee K, Nam GB, Robles R, Schimpf R, Stapleton DD, Viskin S,Winters S, Wolpert C, Zimmern S, Veltmann C, Antzelevitch C. Mutations in thecardiac L-type calcium channel associated with inherited J-wave syndromes andsudden cardiac death. Heart Rhythm. 2010 Dec;7(12):1872-82. doi:10.1016/j.hrthm.2010.08.026. Epub 2010 Oct 14. PubMed PMID: 20817017; PubMedCentral PMCID: PMC2999985.
40. Bénit P, Slama A, Cartault F, Giurgea I, Chretien D, Lebon S, Marsac C,Munnich A, Rötig A, Rustin P. Mutant NDUFS3 subunit of mitochondrial complex Icauses Leigh syndrome. J Med Genet. 2004 Jan;41(1):14-7. PubMed PMID: 14729820;PubMed Central PMCID: PMC1757256.
41. Callewaert BL, Willaert A, Kerstjens-Frederikse WS, De Backer J, Devriendt K, Albrecht B, Ramos-Arroyo MA, Doco-Fenzy M, Hennekam RC, Pyeritz RE, Krogmann ON, Gillessen- kaesbach G, Wakeling EL, Nik-zainal S, Francannet C, Mauran P, Booth C,Barrow M, Dekens R, Loeys BL, Coucke PJ, De Paepe AM. Arterial tortuositysyndrome: clinical and molecular findings in 12 newly identified families. HumMutat. 2008 Jan;29(1):150-8. PubMed PMID: 17935213.
42. Cao H, Alston L, Ruschman J, Hegele RA. Heterozygous CAV1 frameshift mutations(MIM 601047) in patients with atypical partial lipodystrophy andhypertriglyceridemia. Lipids Health Dis. 2008 Jan 31;7:3. doi:10.1186/1476-511X-7-3. PubMed PMID: 18237401; PubMed Central PMCID: PMC2276215.
43. Carballo S, Robinson P, Otway R, Fatkin D, Jongbloed JD, de Jonge N, Blair E, van Tintelen JP, Redwood C, Watkins H. Identification and functionalcharacterization of cardiac troponin I as a novel disease gene in autosomaldominant dilated cardiomyopathy. Circ Res. 2009 Aug 14;105(4):375-82. doi:10.1161/CIRCRESAHA.109.196055. Epub 2009 Jul 9. PubMed PMID: 19590045.
44. Carbone I, Bruno C, Sotgia F, Bado M, Broda P, Masetti E, Panella A, Zara F,Bricarelli FD, Cordone G, Lisanti MP, Minetti C. Mutation in the CAV3 gene causespartial caveolin-3 deficiency and hyperCKemia. Neurology. 2000 Mar28;54(6):1373-6. PubMed PMID: 10746614.
45. Carmignac V, Salih MA, Quijano-Roy S, Marchand S, Al Rayess MM, Mukhtar MM,Urtizberea JA, Labeit S, Guicheney P, Leturcq F, Gautel M, Fardeau M, CampbellKP, Richard I, Estournet B, Ferreiro A. C-terminal titin deletions cause a novel early-onset myopathy with fatal cardiomyopathy. Ann Neurol. 2007Apr;61(4):340-51. Erratum in: Ann Neurol. 2012 May;71(5):728. PubMed PMID:17444505.
46. Carniel E, Taylor MR, Sinagra G, Di Lenarda A, Ku L, Fain PR, Boucek MM,Cavanaugh J, Miocic S, Slavov D, Graw SL, Feiger J, Zhu XZ, Dao D, Ferguson DA,Bristow MR, Mestroni L. Alpha-myosin heavy chain: a sarcomeric gene associatedwith dilated and hypertrophic phenotypes of cardiomyopathy. Circulation. 2005 Jul5;112(1):54-9. PubMed PMID: 15998695.
47. Cecconi M, Parodi MI, Formisano F, Spirito P, Autore C, Musumeci MB, Favale S,Forleo C, Rapezzi C, Biagini E, Davì S, Canepa E, Pennese L, Castagnetta M,Degiorgio D, Coviello DA. Targeted next-generation sequencing helps to decipherthe genetic and phenotypic heterogeneity of hypertrophic cardiomyopathy. Int JMol Med. 2016 Oct;38(4):1111-24. doi: 10.3892/ijmm.2016.2732. Epub 2016 Sep 7.PubMed PMID: 27600940; PubMed Central PMCID: PMC5029966.
48. Cetin N, Balci-Hayta B, Gundesli H, Korkusuz P, Purali N, Talim B, Tan E,Selcen D, Erdem-Ozdamar S, Dincer P. A novel desmin mutation leading to autosomalrecessive limb-girdle muscular dystrophy: distinct histopathological outcomescompared with desminopathies. J Med Genet. 2013 Jul;50(7):437-43. doi:10.1136/jmedgenet-2012-101487. Epub 2013 May 18. PubMed PMID: 23687351.
49. Chantret I, Dupré T, Delenda C, Bucher S, Dancourt J, Barnier A, Charollais A,Heron D, Bader-Meunier B, Danos O, Seta N, Durand G, Oriol R, Codogno P, MooreSE. Congenital disorders of glycosylation type Ig is defined by a deficiency indolichyl-P-mannose:Man7GlcNAc2-PP-dolichyl mannosyltransferase. J Biol Chem. 2002Jul 12;277(28):25815-22. Epub 2002 Apr 30. PubMed PMID: 11983712.
50. Chen L, Lee L, Kudlow BA, Dos Santos HG, Sletvold O, Shafeghati Y, Botha EG,Garg A, Hanson NB, Martin GM, Mian IS, Kennedy BK, Oshima J. LMNA mutations inatypical Werner's syndrome. Lancet. 2003 Aug 9;362(9382):440-5. PubMed PMID:12927431.
51. Chen L, Marquardt ML, Tester DJ, Sampson KJ, Ackerman MJ, Kass RS. Mutation ofan A-kinase-anchoring protein causes long-QT syndrome. Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20990-5. Epub 2007 Dec 19. PubMed PMID: 18093912; PubMedCentral PMCID: PMC2409254.
52. Chen PC, Yin J, Yu HW, Yuan T, Fernandez M, Yung CK, Trinh QM, Peltekova VD,Reid JG, Tworog -Dube E, Morgan MB, Muzny DM, Stein L, McPherson JD, Roberts AE,Gibbs RA, Neel BG, Kucherlapati R. Next-generation sequencing identifies rarevariants associated with Noonan syndrome. Proc Natl Acad Sci U S A. 2014 Aug5;111(31):11473-8. doi: 10.1073/pnas.1324128111. Epub 2014 Jul 21. PubMed PMID:25049390; PubMed Central PMCID: PMC4128129.
53. Choi M, Scholl UI, Yue P, Björklund P, Zhao B, Nelson-Williams C, Ji W, Cho Y,Patel A, Men CJ, Lolis E, Wisgerhof MV, Geller DS, Mane S, Hellman P, Westin G,Åkerström G, Wang W, Carling T, Lifton RP. K+ channel mutations in adrenalaldosterone-producing adenomas and hereditary hypertension. Science. 2011 Feb11;331(6018):768-72. doi: 10.1126/science.1198785. PubMed PMID: 21311022; PubMed Central PMCID: PMC3371087.
54. Colige A, Sieron AL, Li SW, Schwarze U, Petty E, Wertelecki W, Wilcox W,Krakow D, Cohn DH, Reardon W, Byers PH, Lapière CM, Prockop DJ, Nusgens BV. HumanEhlers-Danlos syndrome type VII C and bovine dermatosparaxis are caused bymutations in the procollagen I N-proteinase gene. Am J Hum Genet. 1999Aug;65(2):308-17. PubMed PMID: 10417273; PubMed Central PMCID: PMC1377929.
55. Crane AM, Ledley FD. Clustering of mutations in methylmalonyl CoA mutaseassociated with mut- methylmalonic acidemia. Am J Hum Genet. 1994Jul;55(1):42-50. PubMed PMID: 7912889; PubMed Central PMCID: PMC1918235.
56. Crotti L, Johnson CN, Graf E, De Ferrari GM, Cuneo BF, Ovadia M, PapagiannisJ, Feldkamp MD, Rathi SG, Kunic JD, Pedrazzini M, Wieland T, Lichtner P, BeckmannBM, Clark T, Shaffer C, Benson DW, Kääb S, Meitinger T, Strom TM, Chazin WJ,Schwartz PJ, George AL Jr. Calmodulin mutations associated with recurrent cardiacarrest in infants. Circulation. 2013 Mar 5;127(9):1009-17. doi:10.1161/CIRCULATIONAHA.112.001216. Epub 2013 Feb 6. PubMed PMID: 23388215; PubMedCentral PMCID: PMC3834768.
57. Curran ME, Splawski I, Timothy KW, Vincent GM, Green ED, Keating MT. Amolecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome.Cell. 1995 Mar 10;80(5):795-803. PubMed PMID: 7889573.
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58. Cízková A, Stránecký V, Mayr JA, Tesarová M, Havlícková V, Paul J, Ivánek R,Kuss AW, Hansíková H, Kaplanová V, Vrbacký M, Hartmannová H, Nosková L, Honzík T,Drahota Z, Magner M, Hejzlarová K, Sperl W, Zeman J, Houstek J, Kmoch S. TMEM70mutations cause isolated ATP synthase deficiency and neonatal mitochondrialencephalocardiomyopathy. Nat Genet. 2008 Nov;40(11):1288-90. doi: 10.1038/ng.246.Epub 2008 Oct 26. PubMed PMID: 18953340.
59. Dasgupta C, Martinez AM, Zuppan CW, Shah MM, Bailey LL, Fletcher WH.Identification of connexin43 (alpha1) gap junction gene mutations in patientswith hypoplastic left heart syndrome by denaturing gradient gel electrophoresis(DGGE). Mutat Res. 2001 Aug 8;479(1-2):173-86. PubMed PMID: 11470490.
60. Davis JS, Hassanzadeh S, Winitsky S, Lin H, Satorius C, Vemuri R, Aletras AH, Wen H, Epstein ND. The overall pattern of cardiac contraction depends on aspatial gradient of myosin regulatory light chain phosphorylation. Cell. 2001 Nov30;107(5):631-41. PubMed PMID: 11733062.
61. De Bortoli M, Beffagna G, Bauce B, Lorenzon A, Smaniotto G, Rigato I, CaloreM, Li Mura IE, Basso C, Thiene G, Lanfranchi G, Danieli GA, Nava A, Rampazzo A.The p.A897KfsX4 frameshift variation in desmocollin-2 is not a causative mutationin arrhythmogenic right ventricular cardiomyopathy. Eur J Hum Genet. 2010Jul;18(7):776-82. doi: 10.1038/ejhg.2010.19. Epub 2010 Mar 3. PubMed PMID:20197793; PubMed Central PMCID: PMC2987370.
62. De Sandre-Giovannoli A, Chaouch M, Kozlov S, Vallat JM, Tazir M, Kassouri N,Szepetowski P, Hammadouche T, Vandenberghe A, Stewart CL, G rid D, Lévy N.Homozygous defects in LMNA, encoding lamin A/C nuclear-envelope proteins, causeautosomal recessive axonal neuropathy in human (Charcot-Marie-Tooth disorder type2) and mouse. Am J Hum Genet. 2002 Mar;70(3):726-36. Epub 2002 Jan 17. Erratumin: Am J Hum Genet 2002 Apr;70(4):1075. PubMed PMID: 11799477; PubMed CentralPMCID: PMC384949.
63. Del Bigio MR, Chudley AE, Sarnat HB, Campbell C, Goobie S, Chodirker BN,Selcen D. Infantile muscular dystrophy in Canadian aboriginals is anαB-crystallinopathy. Ann Neurol. 2011 May;69(5):866-71. doi: 10.1002/ana.22331.Epub 2011 Feb 18. PubMed PMID: 21337604; PubMed Central PMCID: PMC3085857.
64. Delpón E, Cordeiro JM, Núñez L, Thomsen PE, Guerchicoff A, Pollevick GD, Wu Y,Kanters JK, Larsen CT, Hofman -Bang J, Burashnikov E, Christiansen M, AntzelevitchC. Functional effects of KCNE3 mutation and its role in the development ofBrugada syndrome. Circ Arrhythm Electrophysiol. 2008 Aug;1(3):209-18. doi:10.1161/CIRCEP.107.748103. Erratum in: Circ Arrhythm Electrophysiol. 2008Aug;1(3):e2. Hofman-Bang, Jacob [added]. PubMed PMID: 19122847; PubMed CentralPMCID: PMC2585750.
65. Demirhan O, Türkmen S, Schwabe GC, Soyupak S, Akgül E, Tastemir D, Karahan D, Mundlos S, Lehmann K. A homozygous BMPR1B mutation causes a new subtype ofacromesomelic chondrodysplasia with genital anomalies. J Med Genet. 2005Apr;42(4):314-7. PubMed PMID: 15805157; PubMed Central PMCID: PMC1736042.
66. Den Dunnen JT, Grootscholten PM, Bakker E, Blonden LA, Ginjaar HB, WapenaarMC, van Paassen HM, van Broeckhoven C, Pearson PL, van Ommen GJ. Topography ofthe Duchenne muscular dystrophy (DMD) gene: FIGE and cDNA analysis of 194 casesreveals 115 deletions and 13 duplications. Am J Hum Genet. 1989 Dec;45(6):835-47.PubMed PMID: 2573997; PubMed Central PMCID: PMC1683480.
67. Desviat LR, Clavero S, Perez-Cerdá C, Navarrete R, Ugarte M, Perez B. Newsplicing mutations in propionic acidemia. J Hum Genet. 2006;51(11):992-7. Epub2006 Oct 19. PubMed PMID: 17051315.
68. Di Natale P, Villani GR, Di Domenico C, Daniele A, Dionisi Vici C, Bartuli A. Analysis of Sanfilippo A gene mutations in a large pedigree. Clin Genet. 2003Apr;63(4):314-8. PubMed PMID: 12702166.
69. Donaldson MR, Jensen JL, Tristani-Firouzi M, Tawil R, Bendahhou S, Suarez WA, Cobo AM, Poza JJ, Behr E, Wagstaff J, Szepetowski P, Pereira S, Mozaffar T,Escolar DM, Fu YH, Ptácek LJ. PIP2 binding residues of Kir2.1 are common targets of mutations causing Andersen syndrome. Neurology. 2003 Jun 10;60(11):1811-6.PubMed PMID: 12796536.
70. Douglas J, Hanks S, Temple IK, Davies S, Murray A, Upadhyaya M, Tomkins S,Hughes HE, Cole TR, Rahman N. NSD1 mutations are the major cause of Sotossyndrome and occur in some cases of Weaver syndrome but are rare in otherovergrowth phenotypes. Am J Hum Genet. 2003 Jan;72(1):132-43. Epub 2002 Dec 2.PubMed PMID: 12464997; PubMed Central PMCID: PMC378618.
71. Doyle AJ, Doyle JJ, Bessling SL, Maragh S, Lindsay ME, Schepers D, Gillis E,Mortier G, Homfray T, Sauls K, Norris RA, Huso ND, Leahy D, Mohr DW, CaulfieldMJ, Scott AF, Destrée A, Hennekam RC, Arn PH, Curry CJ, Van Laer L, McCallion AS,Loeys BL, Dietz HC. Mutations in the TGF-β repressor SKI causeShprintzen-Goldberg syndrome with aortic aneurysm. Nat Genet. 2012Nov;44(11):1249-54. doi: 10.1038/ng.2421. Epub 2012 Sep 30. PubMed PMID:23023332; PubMed Central PMCID: PMC3545695.
72. Drake KM, Zygmunt D, Mavrakis L, Harbor P, Wang L, Comhair SA, Erzurum SC,Aldred MA. Altered MicroRNA processing in herit able pulmonary arterialhypertension: an important role for Smad-8. Am J Respir Crit Care Med. 2011 Dec15;184(12):1400-8. doi: 10.1164/rccm.201106-1130OC. Epub 2011 Sep 15. PubMedPMID: 21920918; PubMed Central PMCID: PMC3262031.
73. Duarri A, Jezierska J, Fokkens M, Meijer M, Schelhaas HJ, den Dunnen WF, vanDijk F, Verschuuren-Bemelmans C, Hageman G, van de Vlies P, Küsters B, van deWarrenburg BP, Kremer B, Wijmenga C, Sinke RJ, Swertz MA, Kampinga HH, Boddeke E,Verbeek DS. Mutations in potassium channel kcnd3 cause spinocerebellar ataxiatype 19. Ann Neurol. 2012 Dec;72(6):870-80. doi: 10.1002/ana.23700. PubMed PMID: 23280838.
74. Duboscq-Bidot L, Xu P, Charron P, Neyroud N, Dilanian G, Millaire A, Bors V,Komajda M, Villard E. Mutations in the Z-band protein myopalladin gene andidiopathic dilated cardiomyopathy. Cardiovasc Res. 2008 Jan;77(1):118-25. Epub2007 Sep 19. PubMed PMID: 18006477.
75. Duff RM, Tay V, Hackman P, Ravenscroft G, McLean C, Kennedy P, Steinbach A,Schöffler W, van der Ven PFM, Fürst DO, Song J, Djinović-Carugo K, Penttilä S,Raheem O, Reardon K, Malandrini A, Gambelli S, Villanova M, Nowak KJ, WilliamsDR, Landers JE, Brown RH Jr, Udd B, Laing NG. Mutations in the N-terminalactin-binding domain of filamin C cause a distal myopathy. Am J Hum Genet. 2011Jun 10;88(6):729-740. doi: 10.1016/j.ajhg.2011.04.021. Epub 2011 May 27. PubMedPMID: 21620354; PubMed Central PMCID: PMC3113346.
76. Dupré T, Vuillaumier-Barrot S, Chantret I, Sadou Yayé H, Le Bizec C, AfenjarA, Altuzarra C, Barnérias C, Burglen L, de Lonlay P, Feillet F, Napuri S, Seta N,Moore SE. Guanosine diphosphate-mannose:GlcNAc2-PP-dolichol mannosyltransferasedeficiency (congenital disorders of glycosylation type Ik): five new patients andseven novel mutations. J Med Genet. 2010 Nov;47(11):729-35. doi:10.1136/jmg.2009.072504. Epub 2010 Aug 2. Erratum in: J Med Genet. 2015Mar;52(3):216. Yayé, H S [corrected to Sadou Yayé, H]. PubMed PMID: 20679665.
77. Dündar M, Müller T, Zhang Q, Pan J, Steinmann B, Vodopiutz J, Gruber R, SonodaT, Krabichler B, Utermann G, Baenziger JU, Zhang L, Janecke AR. Loss ofdermatan-4- sulfotransferase 1 function results in adducted thumb-clubfootsyndrome. Am J Hum Genet. 2009 Dec;85(6):873-82. doi: 10.1016/j.ajhg.2009.11.010.PubMed PMID: 20004762; PubMed Central PMCID: PMC2790573.
78. Echaniz-Laguna A, Ghezzi D, Chassagne M, Mayençon M, Padet S, Melchionda L,Rouvet I, Lannes B, Bozon D, Latour P, Zeviani M, Mousson de Camaret B. SURF1deficiency causes demyelinating Charcot-Marie-Tooth disease. Neurology. 2013 Oct 22;81(17):1523-30. doi: 10.1212/WNL.0b013e3182a4a518. Epub 2013 Sep 11. PubMedPMID: 24027061; PubMed Central PMCID: PMC3888171.
79. Eerola I, Boon LM, Mulliken JB, Burrows PE, Dompmartin A, Watanabe S, VanwijckR, Vikkula M. Capillary malformation -arteriovenous malformation, a new clinicaland genetic disorder caused by RASA1 mutations. Am J Hum Genet. 2003Dec;73(6):1240-9. Epub 2003 Nov 24. PubMed PMID: 14639529; PubMed Central PMCID: PMC1180390.
80. Elstner M, Bettecken T, Wasner M, Anneser F, Dichgans M, Meitinger T, GasserT, Klopstock T. Familial carpal tunnel syndrome: further evidence for a geneticcontribution. Clin Genet. 2006 Feb;69(2):179-82. PubMed PMID: 16433699.
81. Eng CM, Resnick-Silverman LA, Niehaus DJ, Astrin KH, Desnick RJ. Nature andfrequency of mutations in the alpha-galactosidase A gene that cause Fabrydisease. Am J Hum Genet. 1993 Dec;53(6):1186-97. PubMed PMID: 7504405; PubMedCentral PMCID: PMC1682507.
82. Eriksson M, Brown WT, Gordon LB, Glynn MW, Singer J, Scott L, Erdos MR,Robbins CM, Moses TY, Berglund P, Dutra A, Pak E, Durkin S, Csoka AB, Boehnke M, Glover TW, Collins FS. Recurrent de novo point mutations in lamin A causeHutchinson-Gilford progeria syndrome. Nature. 2003 May 15;423(6937):293-8. Epub2003 Apr 25. PubMed PMID: 12714972.
83. Faber CG, Lauria G, Merkies IS, Cheng X, Han C, Ahn HS, Persson AK,Hoeijmakers JG, Gerrits MM, Pierro T, Lombardi R, Kapetis D, Dib-Hajj SD, Waxman SG. Gain-of-function Nav1.8 mutations in painful neuropathy. Proc Natl Acad Sci US A. 2012 Nov 20;109(47):19444-9. doi: 10.1073/pnas.1216080109. Epub 2012 Oct 31.PubMed PMID: 23115331; PubMed Central PMCID: PMC3511073.
84. Fatkin D, MacRae C, Sasaki T, Wolff MR, Porcu M, Frenneaux M, Atherton J,Vidaillet HJ Jr, Spudich S, De Girolami U, Seidman JG, Seidman C, Muntoni F,Müehle G, Johnson W, McDonough B. Missense mutations in the rod domain of thelamin A/C gene as causes of dilated cardiomyopathy and conduction-system disease.N Engl J Med. 1999 Dec 2;341(23):1715-24. PubMed PMID: 10580070.
85. Fisher JH, Miller YE, Sparkes RS, Bateman JB, Kimmel KA, Carey TE, Rodell T,Shoemaker SA, Scoggin CH. Wilms' tumor-aniridia association: segregation ofaffected chromosome in somatic cell hybrids, identification of cell surfaceantigen associated with deleted area, and regional mapping of c-Ha-ras-1oncogene, insulin gene, and beta-globin gene. Somat Cell Mol Genet. 1984Sep;10(5):455-64. PubMed PMID: 6089356.
86. Garcia CK, Wilund K, Arca M, Zuliani G, Fellin R, Maioli M, Calandra S,Bertolini S, Cossu F, Grishin N, Barnes R, Cohen JC, Hobbs HH. Autosomalrecessive hypercholesterolemia caused by mutations in a putative LDL receptoradaptor protein. Science. 2001 May 18;292(5520):1394-8. Epub 2001 Apr 26. PubMed PMID: 11326085.
87. Garg V, Kathiriya IS, Barnes R, Schluterman MK, King IN, Butler CA, RothrockCR, Eapen RS, Hirayama-Yamada K, Joo K, Matsuoka R, Cohen JC, Srivastava D. GATA4mutations cause human congenital heart defects and reveal an interaction withTBX5. Nature. 2003 Jul 24;424(6947):443-7. Epub 2003 Jul 6. PubMed PMID:12845333.
88. Garrido E, Chabás A, Coll MJ, Blanco M, Domínguez C, Grinberg D, Vilageliu L, Cormand B. Identification of the molecular defects in Spanish and Argentinianmucopolysaccharidosis VI (Maroteaux-Lamy syndrome) patients, including 9 novelmutations. Mol Genet Metab. 2007 Sep-Oct;92(1-2):122-30. Epub 2007 Jul 20. PubMedPMID: 17643332.
89. Gavish D, Brinton EA, Breslow JL. Heritable allele-specific differences inamounts of apoB and low-density lipoproteins in plasma. Science. 1989 Apr7;244(4900):72-6. PubMed PMID: 2565046.
90. Gebbia M, Ferrero GB, Pilia G, Bassi MT, Aylsworth A, Penman-Splitt M, BirdLM, Bamforth JS, Burn J, Schlessinger D, Nelson DL, Casey B. X-linked situsabnormalities result from mutations in ZIC3. Nat Genet. 1997 Nov;17(3):305-8.PubMed PMID: 9354794.
91. Geier C, Gehmlich K, Ehler E, Hassfeld S, Perrot A, Hayess K, Cardim N, WenzelK, Erdmann B, Krackhardt F, Posch MG, Osterziel KJ, Bublak A, Nägele H, ScheffoldT, Dietz R, Chien KR, Spuler S, Fürst DO, Nürnberg P, Ozcelik C. Beyond thesarcomere: CSRP3 mutations cause hypertrophic cardiomyopathy. Hum Mol Genet. 2008Sep 15;17(18):2753-65. doi: 10.1093/hmg/ddn160. Epub 2008 May 27. Erratum in: HumMol Genet. 2008 Nov 1;17(21):3436. Osterziel, Karl J [added]. PubMed PMID:18505755.
92. Geisterfer-Lowrance AA, Kass S, Tanigawa G, Vosberg HP, McKenna W, Seidman CE,Seidman JG. A molecular basis for familial hypertrophic cardiomyopathy: a betacardiac myosin heavy chain gene missense mutation. Cell. 1990 Sep7;62(5):999-1006. PubMed PMID: 1975517.
93. Gerull B, Gramlich M, Atherton J, McNabb M, Trombitás K, Sasse-Klaassen S,Seidman JG, Seidman C, Granzier H, Labeit S, Frenneaux M, Thierfelder L.Mutations of TTN, encoding the giant muscle filament titin, cause familialdilated cardiomyopathy. Nat Genet. 2002 Feb;30(2):201-4. Epub 2002 Jan 14. PubMedPMID: 11788824.
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94. Gerull B, Heuser A, Wichter T, Paul M, Basson CT, McDermott DA, Lerman BB,Markowitz SM, Ellinor PT, MacRae CA, Peters S, Grossmann KS, Drenckh ahn J,Michely B, Sasse- Klaassen S, Birchmeier W, Dietz R, Breithardt G, Schulze-Bahr E,Thierfelder L. Mutations in the desmosomal protein plakophilin-2 are common inarrhythmogenic right ventricular cardiomyopathy. Nat Genet. 2004Nov;36(11):1162-4. Epub 2004 Oct 17. Erratum in: Nat Genet. 2005 Jan;37(1):106.PubMed PMID: 15489853.
95. Ghezzi D, Goffrini P, Uziel G, Horvath R, Klopstock T, Lochmüller H, D'AdamoP, Gasparini P, Strom TM, Prokisch H, Invernizzi F, Ferrero I, Zeviani M. SDHAF1,encoding a LYR complex-II specific assembly factor, is mutated in SDH-defectiveinfantile leukoencephalopathy. Nat Genet. 2009 Jun;41(6):654-6. doi:10.1038/ng.378. Epub 2009 May 24. PubMed PMID: 19465911.
96. Giunta C, Elçioglu NH, Albrecht B, Eich G, Chambaz C, Janecke AR, Yeowell H,Weis M, Eyre DR, Kraenzlin M, Steinmann B. Spondylocheiro dysplastic form of the Ehlers-Danlos syndrome--an autosomal-recessive entity caused by mutations in the zinc transporter gene SLC39A13. Am J Hum Genet. 2008 Jun;82(6):1290-305. doi:10.1016/j.ajhg.2008.05.001. PubMed PMID: 18513683; PubMed Central PMCID:PMC2427271.
97. Goker-Alpan O, Giasson BI, Eblan MJ, Nguyen J, Hurtig HI, Lee VM, Trojanowski JQ, Sidransky E. Glucocerebrosidase mutations are an important risk factor forLewy body disorders. Neurology. 2006 Sep 12;67(5):908-10. Epub 2006 Jun 21.PubMed PMID: 16790605.
98. Goldfarb LG, Park KY, Cervenáková L, Gorokhova S, Lee HS, Vasconcelos O, NagleJW, Semino-Mora C, Sivakumar K, Dalakas MC. Missense mutations in desminassociated with familial cardiac and skeletal myopathy. Nat Genet. 1998Aug;19(4):402-3. PubMed PMID: 9697706.
99. Gomez-Hurtado N, Boczek NJ, Kryshtal DO, Johnson CN, Sun J, Nitu FR, CorneaRL, Chazin WJ, Calvert ML, Tester DJ, Ackerman MJ, Knollmann BC. NovelCPVT-Associated Calmodulin Mutation in CALM3 (CALM3-A103V) ActivatesArrhythmogenic Ca Waves and Sparks. Circ Arrhythm Electrophysiol. 2016 Aug;9(8). pii: e004161. doi: 10.1161/CIRCEP.116.004161. PubMed PMID: 27516456; PubMedCentral PMCID: PMC4988333.
100. Gripp KW, Aldinger KA, Bennett JT, Baker L, Tusi J, Powell-Hamilton N, StableyD, Sol-Church K, Timms AE, Dobyns WB. A novel rasopathy caused by recurrent denovo missense mutations in PPP1CB closely resembles Noonan syndrome with looseanagen hair. Am J Med Genet A. 2016 Sep;170(9):2237-47. doi:10.1002/ajmg.a.37781. Epub 2016 Jun 5. PubMed PMID: 27264673; PubMed CentralPMCID: PMC5134331.
101. Gueneau L, Bertrand AT, Jais JP, Salih MA, Stojkovic T, Wehnert M,Hoeltzenbein M, Spuler S, Saitoh S, Verschueren A, Tranchant C, Beuvin M, Lacene E, Romero NB, Heath S, Zelenika D, Voit T, Eymard B, Ben Yaou R, Bonne G.Mutations of the FHL1 gene cause Emery-Dreifuss muscular dystrophy. Am J HumGenet. 2009 Sep;85(3):338-53. doi: 10.1016/j.ajhg.2009.07.015. Epub 2009 Aug 27. PubMed PMID: 19716112; PubMed Central PMCID: PMC2771595.
102. Guo DC, Gong L, Regalado ES, Santos-Cortez RL, Zhao R, Cai B, Veeraraghavan S,Prakash SK, Johnson RJ, Muilenburg A, Willing M, Jondeau G, Boileau C, Pannu H,Moran R, Debacker J; GenTAC Investigators, National Heart, Lung, and BloodInstitute Go Exome Sequencing Project; Montalcino Aortic Con sortium, Bamshad MJ, Shendure J, Nickerson DA, Leal SM, Raman CS, Swindell EC, Milewicz DM. MAT2Amutations predispose individuals to thoracic aortic aneurysms. Am J Hum Genet.2015 Jan 8;96(1):170-7. doi: 10.1016/j.ajhg.2014.11.015. Epub 2014 Dec 31. PubMedPMID: 25557781; PubMed Central PMCID: PMC4289682.
103. Guo DC, Papke CL, Tran-Fadulu V, Regalado ES, Avidan N, Johnson RJ, Kim DH,Pannu H, Willing MC, Sparks E, Pyeritz RE, Singh MN, Dalman RL, Grotta JC, MarianAJ, Boerwinkle EA, Frazier LQ, LeMaire SA, Coselli JS, Estrera AL, Safi HJ,Veeraraghavan S, Muzny DM, Wheeler DA, Willerson JT, Yu RK, Shete SS, Scherer SE,Raman CS, Buja LM, Milewicz DM. Mutations in smooth muscle alpha-actin (ACTA2)cause coronary artery disease, stroke, and Moyamoya disease, along with thoracic aortic disease. Am J Hum Genet. 2009 May;84(5):617-27. doi:10.1016/j.ajhg.2009.04.007. Epub 2009 Apr 30. PubMed PMID: 19409525; PubMedCentral PMCID: PMC2680995.
104. Guo DC, Regalado E, Casteel DE, Santos-Cortez RL, Gong L, Kim JJ, Dyack S,Horne SG, Chang G, Jondeau G, Boileau C, Coselli JS, Li Z, Leal SM, Shendure J,Rieder MJ, Bamshad MJ, Nickerson DA; GenTAC Registry Consortium; National Heart, Lung, and Blood Institute Grand Opportunity Exome Sequencing Project, Kim C,Milewicz DM. Recurrent gain-of-function mutation in PRKG1 causes thoracic aortic aneurysms and acute aortic dissections. Am J Hum Genet. 2013 Aug 8;93(2):398-404.doi: 10.1016/j.ajhg.2013.06.019. Epub 2013 Aug 1. PubMed PMID: 23910461; PubMedCentral PMCID: PMC3738837.
105. Haack TB, Kopajtich R, Freisinger P, Wieland T, Rorbach J, Nicholls TJ,Baruffini E, Walther A, Danhauser K, Zimmermann FA, Hu sain RA, Schum J, Mundy H, Ferrero I, Strom TM, Meitinger T, Taylor RW, Minczuk M, Mayr JA, Prokisch H.ELAC2 mutations cause a mitochondrial RNA processing defect associated withhypertrophic cardiomyopathy. Am J Hum Genet. 2013 Aug 8;93(2):211-23. doi:10.1016/j.ajhg.2013.06.006. Epub 2013 Jul 11. PubMed PMID: 23849775; PubMedCentral PMCID: PMC3738821.
106. Hackman P, Vihola A, Haravuori H, Marchand S, Sarparanta J, De Seze J, Labeit S, Witt C, Peltonen L, Richard I, Udd B. Tibial muscular dystrophy is atitinopathy caused by mutations in TTN, the gene encoding the giantskeletal-muscle protein titin. Am J Hum Genet. 2002 Sep;71(3):492-500. Epub 2002 Jul 26. PubMed PMID: 12145747; PubMed Central PMCID: PMC379188.
107. Hayashi T, Arimura T, Itoh-Satoh M, Ueda K, Hohda S, Inagaki N, Takahashi M,Hori H, Yasunami M, Nishi H, Koga Y, Nakamura H, Matsuzaki M, Choi BY, Bae SW,You CW, Han KH, Park JE, Knöll R, Hoshijima M, Chien KR, Kimura A. Tcap genemutations in hypertrophic cardiomyopathy and dilated cardiomyopathy. J Am CollCardiol. 2004 Dec 7;44(11):2192- 201. PubMed PMID: 15582318.
108. Hayashi T, Arimura T, Ueda K, Shibata H, Hohda S, Takahashi M, Hori H, Koga Y,Oka N, Imaizumi T, Yasunami M, Kimura A. Identification and functional analysisof a caveolin-3 mutation associated with familial hypertrophic cardiomyopathy.Biochem Biophys Res Commun. 2004 Jan 2;313(1):178-84. PubMed PMID: 14672715.
109. Haïssaguerre M, Chatel S, Sacher F, Weerasooriya R, Probst V, Loussouarn G,Horlitz M, Liersch R, Schulze-Bahr E, Wilde A, Kääb S, Koster J, Rudy Y, Le MarecH, Schott JJ. Ventricular fibrillation with prominent early repolarizationassociated with a rare variant of KCNJ8/KATP channel. J CardiovascElectrophysiol. 2009 Jan;20(1):93-8. doi: 10.1111/j.1540- 8167.2008.01326.x.PubMed PMID: 19120683.
110. Hermans MM, Kroos MA, de Graaff E, Oostra BA, Reuser AJ. Two mutationsaffecting the transport and maturation of lysosomal alpha-glucosidase in an adultcase of glycogen storage disease type II. Hum Mutat. 1993;2(4):268-73. PubMedPMID: 8401535.
111. Hoban R, Roberts AE, Demmer L, Jethva R, Shephard B. Noonan syndrome due to a SHOC2 mutation presenting with fetal distress and fatal hypertrophiccardiomyopathy in a premature infant. Am J Med Genet A. 2012 Jun;158A(6):1411-3. doi: 10.1002/ajmg.a.35318. Epub 2012 Apr 23. PubMed PMID: 22528146.
112. Hodgson-Zingman DM, Karst ML, Zingman LV, Heublein DM, Darbar D, Herron KJ,Ballew JD, de Andrade M, Burnett JC Jr, Olson TM. Atrial natriuretic peptideframeshift mutation in familial atrial fibrillation. N Engl J Med. 2008 Jul10;359(2):158-65. doi: 10.1056/NEJMoa0706300. PubMed PMID: 18614783; PubMedCentral PMCID: PMC2518320.
113. Hoefs SJ, Dieteren CE, Distelmaier F, Janssen RJ, Epplen A, Swarts HG, ForkinkM, Rodenburg RJ, Nijtmans LG, Willems PH, Smeitink JA, van den Heuvel LP. NDUFA2 complex I mutation leads to Leigh disease. Am J Hum Genet. 2008Jun;82(6):1306-15. doi: 10.1016/j.ajhg.2008.05.007. PubMed PMID: 18513682; PubMedCentral PMCID: PMC2427319.
114. Hoefs SJ, van Spronsen FJ, Lenssen EW, Nijtmans LG, Rodenburg RJ, Smeitink JA,van den Heuvel LP. NDUFA10 mutations cause comp lex I deficiency in a patient withLeigh disease. Eur J Hum Genet. 2011 Mar;19(3):270-4. doi: 10.1038/ejhg.2010.204.Epub 2010 Dec 8. PubMed PMID: 21150889; PubMed Central PMCID: PMC3061993.
115. Horsthemke B, Beisiegel U, Dunning A, Havinga JR, Williamson R, Humphries S.Unequal crossing -over between two alu-repetitive DNA sequences in thelow-density-lipoprotein- receptor gene. A possible mechanism for the defect in apatient with familial hypercholesterolaemia. Eur J Biochem. 1987 Apr1;164(1):77-81. PubMed PMID: 3549308.
116. Howe JR, Ringold JC, Summers RW, Mitros FA, Nishimura DY, Stone EM. A gene forfamilial juvenile polyposis maps to chromosome 18q21.1. Am J Hum Genet. 1998May;62(5):1129-36. PubMed PMID: 9545410; PubMed Central PMCID: PMC1377097.
117. Huizing M, Iacobazzi V, Ijlst L, Savelkoul P, Ruitenbeek W, van den Heuvel L, Indiveri C, Smeitink J, Trijbels F, Wanders R, Palmieri F. Cloning of the humancarnitine-acylcarnitine carrier cDNA and identification of the molecular defectin a patient. Am J Hum Genet. 1997 Dec;61(6):1239-45. PubMed PMID: 9399886;PubMed Central PMCID: PMC1716087.
118. IJlst L, Ruiter JP, Hoovers JM, Jakobs ME, Wanders RJ. Common missensemutation G1528C in long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency.Characterization and expression of the mutant protein, mutation analysis ongenomic DNA and chromosomal localization of the mitochondrial trifunctionalprotein alpha subunit gene. J Clin Invest. 1996 Aug 15;98(4):1028-33. PubMedPMID: 8770876; PubMed Central PMCID: PMC507519.
119. Ichida F, Tsubata S, Bowles KR, Haneda N, Uese K, Miyawaki T, Dreyer WJ,Messina J, Li H, Bowles NE, Towbin JA. Novel gene mutations in patients with leftventricular noncompaction or Barth syndrome. Circulation. 2001 Mar6;103(9):1256-63. PubMed PMID: 11238270.
120. Inagaki N, Hayashi T, Arimura T, Koga Y, Takahashi M, Shibata H, Teraoka K,Chikamori T, Yamashina A, Kimura A. Alpha B-crystallin mutation in dilatedcardiomyopathy. Biochem Biophys Res Commun. 2006 Apr 7;342(2):379-86. Epub 2006Feb 8. PubMed PMID: 16483541.
121. Ishikawa T, Sato A, Marcou CA, Tester DJ, Ackerman MJ, Crotti L, Schwartz PJ, On YK, Park JE, Nakamura K, Hiraoka M, Nakazawa K, Sakurada H, Arimura T, Makita N, Kimura A. A novel disease gene for Brugada syndrome: sarcolemmalmembrane-associated protein gene mutations impair intracellular trafficking ofhNav1.5. Circ Arrhythm Electrophysiol. 2012 Dec;5(6):1098-107. doi:10.1161/CIRCEP.111.969972. Epub 2012 Oct 12. PubMed PMID: 23064965.
122. Jansen GA, Ofman R, Ferdinandusse S, Ijlst L, Muijsers AO, Skjeldal OH, StokkeO, Jakobs C, Besley GT, Wraith JE, Wanders RJ. Refsum disease is caused bymutations in the phytanoyl-CoA hydroxylase gene. Nat Genet. 1997 Oct;17(2):190-3.PubMed PMID: 9326940.
123. Johansson S, Berland S, Gradek GA, Bongers E, de Leeuw N, Pfundt R, FannemelM, Rødningen O, Brendehaug A, Haukanes BI, Hovland R, Helland G, Houge G.Haploinsufficiency of MEIS2 is associated with orofacial clefting and learningdisability. Am J Med Genet A. 2014 Jul;164A(7):1622-6. doi: 10.1002/ajmg.a.36498.Epub 2014 Mar 26. PubMed PMID: 24678003.
124. Kaler SG, Gallo LK, Proud VK, Percy AK, Mark Y, Segal NA, Goldstein DS, HolmesCS, Gahl WA. Occipital horn syndrome and a mild Menkes phenotype associated with splice site mutations at the MNK locus. Nat Genet. 1994 Oct;8(2):195-202. PubMed PMID: 7842019.
125. Kamisago M, Sharma SD, DePalma SR, Solomon S, Sharma P, McDonough B, Smoot L, Mullen MP, Woolf PK, Wigle ED, Seidman JG, Seidman CE. Mutations in sarcomereprotein genes as a cause of dilated cardiomyopathy. N Engl J Med. 2000 Dec7;343(23):1688-96. PubMed PMID: 11106718.
126. Kappanayil M, Nampoothiri S, Kannan R, Renard M, Coucke P, Malfait F, Menon S,Ravindran HK, Kurup R, Faiyaz-Ul-Haque M, Kumar K, De Paepe A. Characterizationof a distinct lethal arteriopathy syndrome in twenty-two infants associated with an identical, novel mutation in FBLN4 gene, confirms fibulin-4 as a criticaldeterminant of human vascular elastogenesis. Orphanet J Rare Dis. 2012 Sep3;7:61. doi: 10.1186/1750-1172-7-61. PubMed PMID: 22943132; PubMed Central PMCID:PMC3598868.
127. Karkera JD, Lee JS, Roessler E, Banerjee-Basu S, Ouspenskaia MV, Mez J,Goldmuntz E, Bowers P, Towbin J, Belmont JW, Baxevanis AD, Schier AF, Muenke M.Loss-of-function mutations in growth differentiation factor-1 (GDF1) areassociated with congenital heart defects in humans. Am J Hum Genet. 2007Nov;81(5):987-94. Epub 2007 Sep 28. PubMed PMID: 17924340; PubMed Central PMCID: PMC2265655.
128. Kennerson ML, Nicholson GA, Kaler SG, Kowalski B, Mercer JF, Tang J, LlanosRM, Chu S, Takata RI, Speck-Martins CE, Baets J, Almeida-Souza L, Fischer D,Timmerman V, Taylor PE, Scherer SS, Ferguson TA, Bird TD, De Jonghe P, Feely SM, Shy ME, Garbern JY. Missense mutations in the copper transporter gene ATP7A causeX-linked distal hereditary motor neuropathy. Am J Hum Genet. 2010 Mar12;86(3):343-52. doi: 10.1016/j.ajhg.2010.01.027. Epub 2010 Feb 18. PubMed PMID: 20170900; PubMed Central PMCID: PMC2833394.
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www.sema4.com
129. Kluwe L, Friedrich RE, Mautner VF. Allelic loss of the NF1 gene inNF1-associated plexiform neurofibromas. Cancer Genet Cytogenet. 1999Aug;113(1):65-9. PubMed PMID: 10459349. 130. Knowles MR, Leigh MW, Ostrowski LE, Huang L, Carson JL, Hazucha MJ, Yin W,Berg JS, Davis SD, Dell SD, Ferkol TW, Rosenfeld M, Sagel SD, Milla CE, OlivierKN, Turner EH, Lewis
AP, Bamshad MJ, Nickerson DA, Shendure J, Zariwala MA;Genetic Disorders of Mucociliary Clearance Consortium. Exome sequencingidentifies mutations in CCDC114 as a cause of primary ciliary dyskinesia. Am JHum Genet. 2013 Jan 10;92(1):99-106. doi: 10.1016/j.ajhg.2012.11.003. Epub 2012Dec 20. PubMed PMID: 23261302; PubMed Central PMCID: PMC3542458.
131. Knöll R, Postel R, Wang J, Krätzner R, Hennecke G, Vacaru AM, Vakeel P,Schubert C, Murthy K, Rana BK, Kube D, Knöll G, Schäfer K, Hayashi T, Holm T,Kimura A, Schork N, Toliat MR, Nürnberg P, Schultheiss HP, Schaper W, Schaper J, Bos E, Den Hertog J, van Eeden FJ, Peters PJ, Hasenfuss G, Chien KR, Bakkers J.Laminin-alpha4 and integrin-linked kinase mutations cause human cardiomyopathyvia simultaneous defects in cardiomyocytes and endothelial cells. Circulation.2007 Jul 31;116(5):515-25. Epub 2007 Jul 23. PubMed PMID: 17646580.
132. Kobayashi K, Nakahori Y, Miyake M, Matsumura K, Kondo-Iida E, Nomura Y, SegawaM, Yoshioka M, Saito K, Osawa M, Hamano K, Sakakihara Y, Nonaka I, Nakagome Y,Kanazawa I, Nakamura Y, Tokunaga K, Toda T. An ancient retrotransposal insertion causes Fukuyama-type congenital muscular dystrophy. Nature. 1998 Jul23;394(6691):388-92. PubMed PMID: 9690476.
133. Kodera T, Tan FK, Sasaki T, Arnett FC, Bona CA. Association of 5'-untranslatedregion of the Fibrillin-1 gene with Japanese scleroderma. Gene. 2002 Sep4;297(1-2):61-7. PubMed PMID: 12384286.
134. Kodo K, Nishizawa T, Furutani M, Arai S, Yamamura E, Joo K, Takahashi T,Matsuoka R, Yamagishi H. GATA6 mutations cause human cardiac outflow tractdefects by disrupting semaphorin-plexin signaling. Proc Natl Acad Sci U S A. 2009Aug 18;106(33):13933-8. doi: 10.1073/pnas.0904744106. Epub 2009 Aug 4. PubMedPMID: 19666519; PubMed Central PMCID: PMC2728998.
135. Kohda M, Tokuzawa Y, Kishita Y, Nyuzuki H, Moriyama Y, Mizuno Y, Hirata T,Yatsuka Y, Yamashita-Sugahara Y, Nakachi Y, Kato H, Okuda A, Tamaru S, Borna NN, Banshoya K, Aigaki T, Sato-Miyata Y, Ohnuma K, Suzuki T, Nagao A, Maehata H,Matsuda F, Higasa K, Nagasaki M, Yasuda J, Yamamoto M, Fushimi T, Shimura M, Kaiho-Ichimoto K, Harashima H, Yamazaki T, Mori M, Murayama K, Ohtake A, Okazaki Y. A Comprehensive Genomic Analysis Reveals the Genetic Landscape ofMitochondrial Respiratory Chain Complex Deficiencies. PLoS Genet. 2016 Jan7;12(1):e1005679. doi: 10.1371/journal.pgen.1005679. eCollection 2016 Jan. PubMedPMID: 26741492; PubMed Central PMCID: PMC4704781.
136. Kosaki K, Bassi MT, Kosaki R, Lewin M, Belmont J, Schauer G, Casey B.Characterization and mutation analysis of human LEFTY A and LEFTY B, homologuesof murine genes implicated in left-right axis development. Am J Hum Genet. 1999Mar;64(3):712-21. PubMed PMID: 10053005; PubMed Central PMCID: PMC1377788.
137. Kosaki R, Gebbia M, Kosaki K, Lewin M, Bowers P, Towbin JA, Casey B.Left-right axis malformations associated with mutations in ACVR2B, the gene forhuman activin receptor type IIB. Am J Med Genet. 1999 Jan 1;82(1):70-6. PubMedPMID: 9916847.
138. Krantz ID, Colliton RP, Genin A, Rand EB, Li L, Piccoli DA, Spinner NB.Spectrum and frequency of jagged1 (JAG1) mutations in Alagille syndrome patients and their families. Am J Hum Genet. 1998 Jun;62(6):1361-9. PubMed PMID: 9585603; PubMed Central PMCID: PMC1377154.
139. Kyndt F, Gueffet JP, Probst V, Jaafar P, Legendre A, Le Bouffant F, Toquet C, Roy E, McGregor L, Lynch SA, Newbury-Ecob R, Tran V, Young I, Trochu JN, Le MarecH, Schott JJ. Mutations in the gene encoding filamin A as a cause for familialcardiac valvular dystrophy. Circulation. 2007 Jan 2;115(1):40-9. Epub 2006 Dec26. PubMed PMID: 17190868.
140. Körkkö J, Ala-Kokko L, De Paepe A, Nuytinck L, Earley J, Prockop DJ. Analysis of the COL1A1 and COL1A2 genes by PCR amplification and scanning byconformation-sensitive gel electrophoresis identifies only COL1A1 mutations in 15patients with osteogenesis imperfecta type I: identification of common sequences of null-allele mutations. Am J Hum Genet. 1998 Jan;62(1):98-110. PubMed PMID:9443882; PubMed Central PMCID: PMC1376813.
141. Landstrom AP, Weisleder N, Batalden KB, Bos JM, Tester DJ, Ommen SR, WehrensXH, Claycomb WC, Ko JK, Hwang M, Pan Z, Ma J, Ackerman MJ. Mutations inJPH2-encoded junctophilin-2 associated with hypertrophic cardiomyopathy inhumans. J Mol Cell Cardiol. 2007 Jun;42(6):1026-35. Epub 2007 Apr 18. PubMedPMID: 17509612; PubMed Central PMCID: PMC4318564.
142. Lange S, Xiang F, Yakovenko A, Vihola A, Hackman P, Rostkova E, Kristensen J, Brandmeier B, Franzen G, Hedberg B, Gunnarsson LG, Hughes SM, Marchand S,Sejersen T, Richard I, Edström L, Ehler E, Udd B, Gautel M. The kinase domain of titin controls muscle gene expression and protein turnover. Science. 2005 Jun10;308(5728):1599-603. Epub 2005 Mar 31. PubMed PMID: 15802564.
143. Lee SJ, Lee DH, Yoo HW, Koo SK, Park ES, Park JW, Lim HG, Jung SC.Identification and functional analysis of cystathionine beta-synthase genemutations in patients with homocystinuria. J Hum Genet. 2005;50(12):648-54. Epub 2005 Oct 5. PubMed PMID: 16205833.
144. Lefeber DJ, de Brouwer AP, Morava E, Riemersma M, Schuurs-Hoeijmakers JH,Absmanner B, Verrijp K, van den Akker WM, Huijben K, Steenbergen G, van Reeuwijk J, Jozwiak A, Zucker N, Lorber A, Lammens M, Knopf C, van Bokhoven H, GrünewaldS, Lehle L, Kapusta L, Mandel H, Wevers RA. Autosomal recessive dilatedcardiomyopathy due to DOLK mutations results from abnormal dystroglycanO-mannosylation. PLoS Genet. 2011 Dec;7(12):e1002427. doi:10.1371/journal.pgen.1002427. Epub 2011 Dec 29. PubMed PMID: 22242004; PubMedCentral PMCID: PMC3248466.
145. Levitas A, Muhammad E, Harel G, Saada A, Caspi VC, Manor E, Beck JC, SheffieldV, Parvari R. Familial neonatal isolated cardiomyopathy caused by a mutation inthe flavoprotein subunit of succinate dehydrogenase. Eur J Hum Genet. 2010Oct;18(10):1160-5. doi: 10.1038/ejhg.2010.83. Epub 2010 Jun 16. PubMed PMID:20551992; PubMed Central PMCID: PMC2987458.
146. Li D, Tapscoft T, Gonzalez O, Burch PE, Quiñones MA, Zoghbi WA, Hill R,Bachinski LL, Mann DL, Roberts R. Desmin mutation resp onsible for idiopathicdilated cardiomyopathy. Circulation. 1999 Aug 3;100(5):461-4. PubMed PMID:10430757.
147. Liang WC, Mitsuhashi H, Keduka E, Nonaka I, Noguchi S, Nishino I, Hayashi YK. TMEM43 mutations in Emery-Dreifuss muscular dystrophy-related myopathy. AnnNeurol. 2011 Jun;69(6):1005-13. doi: 10.1002/ana.22338. Epub 2011 Mar 9. PubMedPMID: 21391237.
148. Lim SC, Smith KR, Stroud DA, Compton AG, Tucker EJ, Dasvarma A, Gandolfo LC,Marum JE, McKenzie M, Peters HL, Mowat D, Procopis PG, Wilcken B, ChristodoulouJ, Brown GK, Ryan MT, Bahlo M, Thorburn DR. A founder mutation in PET100 causesisolated complex IV deficiency in Lebanese individuals with Leigh syndrome. Am J Hum Genet. 2014 Feb 6;94(2):209-22. doi: 10.1016/j.ajhg.2013.12.015. Epub 2014Jan 23. PubMed PMID: 24462369; PubMed Central PMCID: PMC3928654.
149. Loeffen J, Smeitink J, Triepels R, Smeets R, Schuelke M, Sengers R, TrijbelsF, Hamel B, Mullaart R, van den Heuvel L. The first nuclear-encoded complex Imutation in a patient with Leigh syndrome. Am J Hum Genet. 1998Dec;63(6):1598-608. PubMed PMID: 9837812; PubMed Central PMCID: PMC1377631.
150. Loeys BL, Chen J, Neptune ER, Judge DP, Podowski M, Holm T, Meyers J, LeitchCC, Katsanis N, Sharifi N, Xu FL, Myers LA, Spevak PJ, Cameron DE, De Backer J,Hellemans J, Chen Y, Davis EC, Webb CL, Kress W, Coucke P, Rifkin DB, De PaepeAM, Dietz HC. A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nat Genet. 2005Mar;37(3):275-81. Epub 2005 Jan 30. PubMed PMID: 15731757.
151. Loh ML, Sakai DS, Flotho C, Kang M, Fliegauf M, Archambeault S, Mullighan CG, Chen L, Bergstraesser E, Bueso-Ramos CE, Emanuel PD, Hasle H, Issa JP, van denHeuvel-Eibrink MM, Locatelli F, Stary J, Trebo M, Wlodarski M, Zecca M, ShannonKM, Niemeyer CM. Mutations in CBL occur frequently in juvenile myelomonocyticleukemia. Blood. 2009 Aug 27;114(9):1859-63. doi: 10.1182/blood-2009-01-198416.Epub 2009 Jul 1. PubMed PMID: 19571318; PubMed Central PMCID: PMC2738571.
152. Lossos A, Meiner Z, Barash V, Soffer D, Schlesinger I, Abramsky O, Argov Z,Shpitzen S, Meiner V. Adult polyglucosan body disease in Ashkenazi Jewishpatients carrying the Tyr329Ser mutation in the glycogen-branching enzyme gene.Ann Neurol. 1998 Dec;44(6):867-72. PubMed PMID: 9851430.
153. Luxán G, Casanova JC, Martínez-Poveda B, Prados B, D'Amato G, MacGrogan D,Gonzalez-Rajal A, Dobarro D, Torroja C, Martinez F, Izquierdo-García JL,Fernández-Friera L, Sabater-Molina M, Kong YY, Pizarro G, Ibañez B, Medrano C,García-Pavía P, Gimeno JR, Monserrat L, Jiménez-Borreguero LJ, de la Pompa JL.Mutations in the NOTCH pathway regulator MIB1 cause left ventricularnoncompaction cardiomyopathy. Nat Med. 2013 Feb;19(2):193-201. doi:10.1038/nm.3046. Epub 2013 Jan 13. PubMed PMID: 23314057.
154. Ma L, Roman-Campos D, Austin ED, Eyries M, Sampson KS, Soubrier F, Germain M, Trégouët DA, Borczuk A, Rosenzweig EB, Girerd B, Montani D, Humbert M, Loyd JE,Kass RS, Chung WK. A novel channelopathy in pulmonary arterial hypertension. NEngl J Med. 2013 Jul 25;369(4):351-361. doi: 10.1056/NEJMoa1211097. PubMed PMID: 23883380; PubMed Central PMCID: PMC3792227.
155. Makita N, Yagihara N, Crotti L, Johnson CN, Beckmann BM, Roh MS, Shigemizu D, Lichtner P, Ishikawa T, Aiba T, Homfray T, Behr ER, Klug D, Denjoy I, MastantuonoE, Theisen D, Tsunoda T, Satake W, Toda T, Nakagawa H, Tsuji Y, Tsuchiya T,Yamamoto H, Miyamoto Y, Endo N, Kimura A, Ozaki K, Motomura H, Suda K, Tanaka T, Schwartz PJ, Meitinger T, Kääb S, Guicheney P, Shimizu W, Bhuiyan ZA, Watanabe H,Chazin WJ, George AL Jr. Novel calmodulin mutations associated with congenitalarrhythmia susceptibility. Circ Cardiovasc Genet. 2014 Aug;7(4):466-74. doi:10.1161/CIRCGENETICS.113.000459. Epub 2014 Jun 10. PubMed PMID: 24917665; PubMed Central PMCID: PMC4140998.
156. Marston S, Montgiraud C, Munster AB, Copeland O, Choi O, Dos Remedios C,Messer AE, Ehler E, Knöll R. OBSCN Mutations Associated with DilatedCardiomyopathy and Haploinsufficiency. PLoS One. 2015 Sep 25;10(9):e0138568. doi:10.1371/journal.pone.0138568. eCollection 2015. PubMed PMID: 26406308; PubMedCentral PMCID: PMC4583186.
157. Maslen CL, Babcock D, Robinson SW, Bean LJ, Dooley KJ, Willour VL, Sherman SL.CRELD1 mutations contribute to the occurrence of cardiac atrioventricular septal defects in Down syndrome. Am J Med Genet A. 2006 Nov 15;140(22):2501-5. PubMedPMID: 17036335.
158. Matsson H, Eason J, Bookwalter CS, Klar J, Gustavsson P, Sunnegårdh J, EnellH, Jonzon A, Vikkula M, Gutierrez I, Granados-Riveron J, Pope M, Bu'Lock F, CoxJ, Robinson TE, Song F, Brook DJ, Marston S, Trybus KM, Dahl N. Alpha-cardiacactin mutations produce atrial septal defects. Hum Mol Genet. 2008 Jan15;17(2):256-65. Epub 2007 Oct 18. PubMed PMID: 17947298.
159. Matthijs G, Schollen E, Pardon E, Veiga-Da-Cunha M, Jaeken J, Cassiman JJ, VanSchaftingen E. Mutations in PMM2, a phosphomannomutase gene on chromosome 16p13, in carbohydrate-deficient glycoprotein type I syndrome (Jaeken syndrome). NatGenet. 1997 May;16(1):88-92. Erratum in: Nat Genet 1997 Jul;16(3):316. PubMedPMID: 9140401.
160. Mayr JA, Haack TB, Graf E, Zimmermann FA, Wieland T, Haberberger B,Superti-Furga A, Kirschner J, Steinmann B, Baumgartner MR, Moroni I, Lamantea E, Zeviani M, Rodenburg RJ, Smeitink J, Strom TM, Meitinger T, Sperl W, Prokisch H. Lack of the mitochondrial protein acylglycerol kinase causes Sengers syndrome. AmJ Hum Genet. 2012 Feb 10;90(2):314-20. doi: 10.1016/j.ajhg.2011.12.005. Epub 2012Jan 26. PubMed PMID: 22284826; PubMed Central PMCID: PMC3276657.
161. McAllister KA, Grogg KM, Johnson DW, Gallione CJ, Baldwin MA, Jackson CE,Helmbold EA, Markel DS, McKinnon WC, Murrell J, et al. Endoglin, a TGF-betabinding protein of endothelial cells, is the gene for hereditary haemorrhagictelangiectasia type 1. Nat Genet. 1994 Dec;8(4):345-51. PubMed PMID: 7894484.
162. McBride KL, Riley MF, Zender GA, Fitzgerald-Butt SM, Towbin JA, Belmont JW,Cole SE. NOTCH1 mutations in individuals with left ventricular outflow tractmalformations redu ce ligand-induced signaling. Hum Mol Genet. 2008 Sep15;17(18):2886-93. doi: 10.1093/hmg/ddn187. Epub 2008 Jun 30. PubMed PMID:18593716; PubMed Central PMCID: PMC2722892.
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163. McKoy G, Protonotarios N, Crosby A, Tsatsopoulou A, Anastasakis A, Coonar A,Norman M, Baboonian C, Jeffery S, McKenna WJ. Identification of a deletion inplakoglobin in arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease). Lancet. 2000 Jun17;355(9221):2119-24. PubMed PMID: 10902626.
164. Medeiros-Domingo A, Kaku T, Tester DJ, Iturralde-Torres P, Itty A, Ye B,Valdivia C, Ueda K, Canizales-Quinteros S, Tusié-Luna MT, Makielski JC, Ackerman MJ. SCN4B-encoded sodium channel beta4 subunit in congenital long-QT syndrome.Circulation. 2007 Jul 10;116(2):134-42. Epub 2007 Jun 25. PubMed PMID: 17592081; PubMed Central PMCID: PMC3332546.
165. Meder B, Haas J, Keller A, Heid C, Just S, Borries A, Boisguerin V,Scharfenberger-Schmeer M, Stähler P, Beier M, Weichenhan D, Strom TM, Pfeufer A, Korn B, Katus HA, Rottbauer
W. Targeted next-generation sequencing for themolecular genetic diagnostics of cardiomyopathies. Circ Cardiovasc Genet. 2011Apr;4(2):110-22. doi: 10.1161/CIRCGENETICS.110.958322. Epub 2011 Jan 20. PubMedPMID: 21252143.
166. Mercuri E, Poppe M, Quinlivan R, Messina S, Kinali M, Demay L, Bourke J,Richard P, Sewry C, Pike M, Bonne G, Muntoni F, Bushby K. Extreme variability of phenotype in patients with an identical missense mutation in the lamin A/C gene: from congenital onset with severe phenotype to milder classic Emery-Dreifussvariant. Arch Neurol. 2004 May;61(5):690-4. PubMed PMID: 15148145.
167. Meredith C, Herrmann R, Parry C, Liyanage K, Dye DE, Durling HJ, Duff RM,Beckman K, de Visser M, van der Graaff MM, Hedera P, Fink JK, Petty EM, Lamon t P,Fabian V, Bridges L, Voit T, Mastaglia FL, Laing NG. Mutations in the slowskeletal muscle fiber myosin heavy chain gene (MYH7) cause laing early-onsetdistal myopathy (MPD1). Am J Hum Genet. 2004 Oct;75(4):703-8. Epub 2004 Aug 20.PubMed PMID: 15322983; PubMed Central PMCID: PMC1182058.
168. Mihalik SJ, Morrell JC, Kim D, Sacksteder KA, Watkins PA, Gould SJ.Identification of PAHX, a Refsum disease gene. Nat Genet. 1997 Oct;17(2):185-9.PubMed PMID: 9326939. 169. Milewicz DM, Østergaard JR, Ala-Kokko LM, Khan N, Grange DK, Mendoza-LondonoR, Bradley TJ, Olney AH, Adès L, Maher JF, Guo D, Buja LM, Kim D, Hyland JC,Regalado ES. De
novo ACTA2 mutation causes a novel syndrome of multisystemicsmooth muscle dysfunction. Am J Med Genet A. 2010 Oct;152A(10):2437-43. doi:10.1002/ajmg.a.33657. PubMed PMID: 20734336; PubMed Central PMCID: PMC3573757.
170. Minetti C, Sotgia F, Bruno C, Scartezzini P, Broda P, Bado M, Masetti E,Mazzocco M, Egeo A, Donati MA, Volonte D, Galbiati F, Cordone G, Bricarelli FD,Lisanti MP, Zara F. Mutations in the caveolin-3 gene cause autosomal dominantlimb-girdle muscular dystrophy. Nat Genet. 1998 Apr;18(4):365-8. PubMed PMID:9537420.
171. Mirza M, Marston S, Willott R, Ashley C, Mogensen J, McKenna W, Robinson P,Redwood C, Watkins H. Dilated cardiomyopathy mutations in three thin filamentregulatory proteins result in a common functional phenotype. J Biol Chem. 2005Aug 5;280(31):28498-506. Epub 2005 May 27. PubMed PMID: 15923195.
172. Mogensen J, Murphy RT, Shaw T, Bahl A, Redwood C, Watkins H, Burke M, Elliott PM, McKenna WJ. Severe disease expression of cardiac troponin C and T mutationsin patients with idiopathic dilated cardiomyopathy. J Am Coll Cardiol. 2004 Nov16;44(10):2033-40. PubMed PMID: 15542288.
173. Mohapatra B, Casey B, Li H, Ho-Dawson T, Smith L, Fernbach SD, Molinari L,Niesh SR, Jefferies JL, Craigen WJ, Towbin JA, Belmont JW, Ware SM.Identification and functional characterization of NODAL rare variants inheterotaxy and isolated cardiovascular malformations. Hum Mol Genet. 2009 Mar1;18(5):861-71. doi: 10.1093/hmg/ddn411. Epub 2008 Dec 8. PubMed PMID: 19064609; PubMed Central PMCID: PMC2722226.
174. Mohler PJ, Le Scouarnec S, Denjoy I, Lowe JS, Guicheney P, Caron L, DriskellIM, Schott JJ, Norris K, Leenhardt A, Kim RB, Escande D, Roden DM. Defining thecellular phenotype of "ankyrin-B syndrome" variants: human ANK2 variantsassociated with clinical phenotypes display a spectrum of activities incardiomyocytes. Circulation. 2007 Jan 30;115(4):432-41. Epub 2007 Jan 22. PubMed PMID: 17242276.
175. Monserrat L, Hermida-Prieto M, Fernandez X, Rodríguez I, Dumont C, Cazón L,Cuesta MG, Gonzalez-Juanatey C, Peteiro J, Alvarez N, Penas-Lado M, Castro-BeirasA. Mutation in the alpha-cardiac actin gene associated with apical hypertrophiccardiomyopathy, left ventricular non-compaction, and septal defects. Eur Heart J.2007 Aug;28(16):1953-61. Epub 2007 Jul 4. PubMed PMID: 17611253.
176. Moreira ES, Wiltshire TJ, Faulkner G, Nilforoushan A, Vainzof M, Suzuki OT,Valle G, Reeves R, Zatz M, Passos-Bueno MR, Jenne DE. Limb-girdle musculardystrophy type 2G is caused by mutations in the gene encoding the sarcomericprotein telethonin. Nat Genet. 2000 Feb;24(2):163-6. PubMed PMID: 10655062.
177. Morita H, Rehm HL, Menesses A, McDonough B, Roberts AE, Kucherlapati R, TowbinJA, Seidman JG, Seidman CE. Shared genetic causes of cardiac hypertrophy inchildren and adults. N Engl J Med. 2008 May 1;358(18):1899-908. doi:10.1056/NEJMoa075463. Epub 2008 Apr 9. PubMed PMID: 18403758; PubMed CentralPMCID: PMC2752150.
178. Moulik M, Vatta M, Witt SH, Arola AM, Murphy RT, McKenna WJ, Boriek AM, Oka K,Labeit S, Bowles NE, Arimura T, Kimura A, Towbin JA. ANKRD1, the gene encodingcardiac ankyrin repeat protein, is a novel dilated cardiomyopathy gene. J Am CollCardiol. 2009 Jul 21;54(4):325-33. doi: 10.1016/j.jacc.2009.02.076. PubMed PMID: 19608030; PubMed Central PMCID: PMC2915893.
179. Muhammad E, Levitas A, Singh SR, Braiman A, Ofir R, Etzion S, Sheffield VC,Etzion Y, Carrier L, Parvari R. PLEKHM2 mutation leads to abnormal localizationof lysosomes, impaired autophagy flux and associates with recessive dilatedcardiomyopathy and left ventricular noncompaction. Hum Mol Genet. 2015 Dec20;24(25):7227-40. doi: 10.1093/hmg/ddv423. Epub 2015 Oct 12. PubMed PMID:26464484; PubMed Central PMCID: PMC4664165.
180. Muntoni F, Cau M, Ganau A, Congiu R, Arvedi G, Mateddu A, Marrosu MG,Cianchetti C, Realdi G, Cao A, et al. Brief report: deletion of the dystrophinmuscle-promoter region associated with X-linked dilated cardiomyopathy. N Engl J Med. 1993 Sep 23;329(13):921-5. PubMed PMID: 8361506.
181. Murakami T, Hayashi YK, Noguchi S, Ogawa M, Nonaka I, Tanabe Y, Ogino M,Takada F, Eriguchi M, Kotooka N, Campbell KP, Osawa M, Nishino I. Fukutin genemutations cause dilated cardiomyopathy with minimal muscle weakness. Ann Neurol. 2006 Nov;60(5):597-602. PubMed PMID: 17036286.
182. Navarro CL, De Sandre-Giovannoli A, Bernard R, Boccaccio I, Boyer A, GenevièveD, Hadj-Rabia S, Gaudy-Marqueste C, Smitt HS, Vabres P, Faivre L, Verloes A, Van Essen T, Flori E, Hennekam R, Beemer FA, Laurent N, Le Merrer M, Cau P, Lévy N.Lamin A and ZMPSTE24 (FACE-1) defects cause nuclear disorganization and identify restrictive dermopathy as a lethal neonatal laminopathy. Hum Mol Genet. 2004 Oct 15;13(20):2493-503. Epub 2004 Aug 18. PubMed PMID: 15317753.
183. Nezu J, Tamai I, Oku A, Ohashi R, Yabuuchi H, Hashimoto N, Nikaido H, Sai Y,Koizumi A, Shoji Y, Takada G, Matsuishi T, Yoshin o M, Kato H, Ohura T, Tsujimoto G, Hayakawa J, Shimane M, Tsuji A. Primary systemic carnitine deficiency iscaused by mutations in a gene encoding sodium ion-dependent carnitinetransporter. Nat Genet. 1999 Jan;21(1):91-4. PubMed PMID: 9916797.
184. Nigro V, de Sá Moreira E, Piluso G, Vainzof M, Belsito A, Politano L, Puca AA,Passos-Bueno MR, Zatz M. Autosomal recessive limb-girdle muscular dystrophy,LGMD2F, is caused by a mutation in the delta-sarcoglycan gene. Nat Genet. 1996Oct;14(2):195-8. PubMed PMID: 8841194.
185. Nishino I, Fu J, Tanji K, Yamada T, Shimojo S, Koori T, Mora M, Riggs JE, OhSJ, Koga Y, Sue CM, Yamamoto A, Murakami N, Shanske S, Byrne E, Bonilla E, NonakaI, DiMauro S, Hirano M. Primary LAMP-2 deficiency causes X-linked vacuolarcardiomyopathy and myopathy (Danon disease). Nature. 2000 Aug24;406(6798):906-10. PubMed PMID: 10972294.
186. Norton N, Li D, Rieder MJ, Siegfried JD, Rampersaud E, Züchner S, Mangos S,Gonzalez-Quintana J, Wang L, McGee S, Reiser J, Martin E, Nickerson DA,Hershberger RE. Genome- wide studies of copy number variation and exome sequencingidentify rare variants in BAG3 as a cause of dilated cardiomyopathy. Am J HumGenet. 2011 Mar 11;88(3):273-82. doi: 10.1016/j.ajhg.2011.01.016. Epub 2011 Feb25. PubMed PMID: 21353195; PubMed Central PMCID: PMC3059419.
187. Novelli G, Muchir A, Sangiuolo F, Helbling-Leclerc A, D'Apice MR, Massart C,Capon F, Sbraccia P, Federici M, Lauro R, Tudisco C, Pallotta R, Scarano G,Dallapiccola B, Merlini L, Bonne G. Mandibuloacral dysplasia is caused by amutation in LMNA-encoding lamin A/C. Am J Hum Genet. 2002 Aug;71(2):426-31. Epub 2002 Jun 19. PubMed PMID: 12075506; PubMed Central PMCID: PMC379176.
188. Ohno S, Zankov DP, Ding WG, Itoh H, Makiyama T, Doi T, Shizuta S, Hattori T,Miyamoto A, Naiki N, Hancox JC, Matsuura H, Horie M. KCNE5 (KCNE1L) variants are novel modulators of Brugada syndrome and idiopathic ventricular fibrillation.Circ Arrhythm Electrophysiol. 2011 Jun;4(3):352-61. doi:10.1161/CIRCEP.110.959619. Epub 2011 Apr 14. PubMed PMID: 21493962.
189. Oliveira C, Westra JL, Arango D, Ollikainen M, Domingo E, Ferreira A, Velho S,Niessen R, Lagerstedt K, Alhopuro P, Laiho P, Veiga I, Teixeira MR, Ligtenberg M,Kleibeuker JH, Sijmons RH, Plukker JT, Imai K, Lage P, Hamelin R, Albuquerque C, Schwartz S Jr, Lindblom A, Peltomaki P, Yamamoto H, Aaltonen LA, Seruca R,Hofstra RM. Distinct patterns of KRAS mutations in colorectal carcinomasaccording to germline mismatch repair defects and hMLH1 methylation status. HumMol Genet. 2004 Oct 1;13(19):2303-11. Epub 2004 Aug 4. PubMed PMID: 15294875.
190. Olson TM, Alekseev AE, Moreau C, Liu XK, Zingman LV, Miki T, Seino S,Asirvatham SJ, Jahangir A, Terzic A. KATP channel mutation confers risk for vein of Marsh all adrenergic atrial fibrillation. Nat Clin Pract Cardiovasc Med. 2007Feb;4(2):110-6. PubMed PMID: 17245405; PubMed Central PMCID: PMC2013306.
191. Olson TM, Illenberger S, Kishimoto NY, Huttelmaier S, Keating MT, Jockusch BM.Metavinculin mutations alter actin interaction in dilated cardiomyopathy.Circulation. 2002 Jan 29;105(4):431-7. PubMed PMID: 11815424.
192. Olson TM, Karst ML, Whitby FG, Driscoll DJ. Myosin light chain mutation causesautosomal recessive cardiomyopathy with mid-cavitary hypertrophy and restrictive physiology. Circulation. 2002 May 21;105(20):2337-40. PubMed PMID: 12021217.
193. Olson TM, Kishimoto NY, Whitby FG, Michels VV. Mutations that alter thesurface charge of alpha-tropomyosin are associated with dilated cardiomyopathy. JMol Cell Cardiol. 2001 Apr;33(4):723-32. PubMed PMID: 11273725.
194. Olson TM, Michels VV, Thibodeau SN, Tai YS, Keating MT. Actin mutations indilated cardiomyopathy, a heritable form of heart failure. Science. 1998 May1;280(5364):750-2. PubMed PMID: 9563954.
195. Osio A, Tan L, Chen SN, Lombardi R, Nagueh SF, Shete S, Roberts R, WillersonJT, Marian AJ. Myozenin 2 is a novel gene for human hypertrophic cardiomyopathy. Circ Res. 2007 Mar 30;100(6):766-8. Epub 2007 Mar 8. PubMed PMID: 17347475;PubMed Central PMCID: PMC2775141.
196. Ostergaard E, Rodenburg RJ, van den Brand M, Thomsen LL, Duno M, Batbayli M,Wibrand F, Nijtmans L. Respiratory chain complex I deficiency due to NDUFA12mutations as a new cause of Leigh syndrome. J Med Genet. 2011 Nov;48(11):737-40. doi: 10.1136/jmg.2011.088856. Epub 2011 May 26. PubMed PMID: 21617257.
197. Pauli S, von Velsen N, Burfeind P, Steckel M, Mänz J, Buchholz A, Borozdin W, Kohlhase J. CHD7 mutations causing CHARGE syndrome are predominantly of paternal origin. Clin Genet. 2012 Mar;81(3):234-9. doi: 10.1111/j.1399-0004.2011.01701.x. Epub 2011 May 27. PubMed PMID: 21554267.
198. Pegoraro E, Gavassini BF, Borsato C, Melacini P, Vianello A, Stramare R,Cenacchi G, Angelini C. MYH7 gene mutation in myosin storage myopathy andscapulo-peroneal myopathy. Neuromuscul Disord. 2007 Apr;17(4):321-9. Epub 2007Mar 2. PubMed PMID: 17336526.
199. Pepin M, Schwarze U, Superti-Furga A, Byers PH. Clinical and genetic features of Ehlers-Danlos syndrome type IV, the vascular type. N Engl J Med. 2000 Mar9;342(10):673-80. Erratum in: N Engl J Med 2001 Feb 1;344(5):392. PubMed PMID:10706896.
200. Pizzuti A, Sarkozy A, Newton AL, Conti E, Flex E, Digilio MC, Amati F, Gianni D, Tandoi C, Marino B, Crossley M, Dallapiccola B. Mutations of ZFPM2/FOG2 genein sporadic cases of tetralogy of Fallot. Hum Mutat. 2003 Nov;22(5):372-7. PubMedPMID: 14517948.
Mail: One Gustave L. Levy Place, Box 1497 Specimens: 1428 Madison Ave, Atran Bldg, Rm 2-25
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201. Poetter K, Jiang H, Hassanzadeh S, Master SR, Chang A, Dalakas MC, Rayment I, Sellers JR, Fananapazir L, Epstein ND. Mutations in either the essential orregulatory light chains of myosin are associated with a rare myopathy in humanheart and skeletal muscle. Nat Genet. 1996 May;13(1):63-9. PubMed PMID: 8673105.
202. Priori SG, Napolitano C, Tiso N, Memmi M, Vignati G, Bloise R, Sorrentino V,Danieli GA. Mutations in the cardiac ryanodine receptor gene (hRyR2) underliecatech olaminergic polymorphic ventricular tachycardia. Circulation. 2001 Jan16;103(2):196-200. PubMed PMID: 11208676.
203. Putnam EA, Zhang H, Ramirez F, Milewicz DM. Fibrillin-2 (FBN2) mutationsresult in the Marfan-like disorder, congenital contractural arachnodactyly. NatGenet. 1995 Dec;11(4):456-8. PubMed PMID: 7493032.
204. Rampazzo A, Nava A, Malacrida S, Beffagna G, Bauce B, Rossi V, Zimbello R,Simionati B, Basso C, Thiene G, Towbin JA, Danieli GA. Mutation in humandesmoplakin domain binding to plakoglobin causes a dominant form ofarrhythmogenic right ventricular cardiomyopathy. Am J Hum Genet. 2002Nov;71(5):1200-6. Epub 2002 Oct 8. PubMed PMID: 12373648; PubMed Central PMCID:PMC385098.
205. Razzaque MA, Nishizawa T, Komoike Y, Yagi H, Furutani M, Amo R, Kamisago M,Momma K, Katayama H, Nakagawa M, Fujiwara Y, Matsu shima M, Mizuno K, Tokuyama M, Hirota H, Muneuchi J, Higashinakagawa T, Matsuoka R. Germline gain-of-functionmutations in RAF1 cause Noonan syndrome. Nat Genet. 2007 Aug;39(8):1013-7. Epub2007 Jul 1. PubMed PMID: 17603482.
206. Renou L, Stora S, Yaou RB, Volk M, Sinkovec M, Demay L, Richard P, Peterlin B,Bonne G. Heart-hand syndrome of Slovenian type: a new kind of laminopathy. J Med Genet. 2008 Oct;45(10):666-71. doi: 10.1136/jmg.2008.060020. Epub 2008 Jul 8.PubMed PMID: 18611980.
207. Roberts AE, Araki T, Swanson KD, Montgomery KT, Schiripo TA, Joshi VA, Li L,Yassin Y, Tamburino AM, Neel BG, Kucherlap ati RS. Germline gain-of-functionmutations in SOS1 cause Noonan syndrome. Nat Genet. 2007 Jan;39(1):70-4. Epub2006 Dec 3. PubMed PMID: 17143285.
208. Roder C, Peters V, Kasuya H, Nishizawa T, Wakita S, Berg D, Schulte C, Khan N,Tatagiba M, Krischek B. Analysis of ACTA2 in European Moyamoya disease patients. Eur J Paediatr Neurol. 2011 Mar;15(2):117-22. doi: 10.1016/j.ejpn.2010.09.002.Epub 2010 Oct 20. PubMed PMID: 20970362.
209. Rodriguez G, Ueyama T, Ogata T, Czernuszewicz G, Tan Y, Dorn GW 2nd, Bogaev R,Amano K, Oh H, Matsubara H, Willerson JT, Marian AJ. Molecular genetic andfunctional characterization implicate muscle-restricted coiled-coil gene (MURC)as a causal gene for familial dilated cardiomyopathy. Circ Cardiovasc Genet. 2011Aug 1;4(4):349-58. doi: 10.1161/CIRCGENETICS.111.959866. Epub 2011 Jun 3. PubMed PMID: 21642240; PubMed Central PMCID: PMC3157556.
210. Rodriguez-Viciana P, Tetsu O, Tidyman WE, Estep AL, Conger BA, Cruz MS,McCormick F, Rauen KA. Germline mutations in genes within the MAPK pathway cause cardio-facio- cutaneous syndrome. Science. 2006 Mar 3;311(5765):1287-90. Epub 2006Jan 26. PubMed PMID: 16439621.
211. Roux-Buisson N, Cacheux M, Fourest-Lieuvin A, Fauconnier J, Brocard J, Denjoy I, Durand P, Guicheney P, Kyndt F, Leenhardt A, Le Marec H, Lucet V, Mabo P,Probst V, Monnier N, Ray PF, Santoni E, Trémeaux P, Lacampagne A, Fauré J,Lunardi J, Marty I. Absence of triadin, a protein of the calcium release complex,is responsible for cardiac arrhythmia with sudden death in human. Hum Mol Genet. 2012 Jun 15;21(12):2759-67. doi: 10.1093/hmg/dds104. Epub 2012 Mar 14. PubMedPMID: 22422768; PubMed Central PMCID: PMC3363337.
212. Sakazume S, Okamoto N, Yamamoto T, Kurosawa K, Numabe H, Ohashi Y, Kako Y,Nagai T, Ohashi H. GPC3 mutations in seven patients with Simpson-Golabi-Behmelsyndrome. Am J Med Genet A. 2007 Aug 1;143A(15):1703-7. PubMed PMID: 17603795.
213. Santamaria R, Blanco M, Chabás A, Grinberg D, Vilageliu L. Identification of14 novel GLB1 mutations, including five deletions, in 19 patients with GM1gangliosidosis from South America. Clin Genet. 2007 Mar;71(3):273-9. PubMed PMID:17309651.
214. Saraiva MJ. Transthyretin mutations in hyperthyroxinemia and amyloid diseases.Hum Mutat. 2001 Jun;17(6):493-503. Review. PubMed PMID: 11385707. 215. Sarkozy A, Carta C, Moretti S, Zampino G, Digilio MC, Pantaleoni F, Scioletti AP, Esposito G, Cordeddu V, Lepri F, Petrangeli V, Dentici ML, Mancini GM,Selicorni A, Rossi C, Mazzanti
L, Marino B, Ferrero GB, Silengo MC, Memo L,Stanzial F, Faravelli F, Stuppia L, Puxeddu E, Gelb BD, Dallapiccola B, TartagliaM. Germline BRAF mutations in Noonan, LEOPARD, and cardiofaciocutaneoussyndromes: molecular diversity and associated phenotypic spectrum. Hum Mutat.2009 Apr;30(4):695-702. doi: 10.1002/humu.20955. PubMed PMID: 19206169; PubMedCentral PMCID: PMC4028130.
216. Satoh M, Takahashi M, Sakamoto T, Hiroe M, Marumo F, Kimura A. Structuralanalysis of the titin gene in hypertrophic cardiomyopathy: identification of anovel disease gene. Biochem Biophys Res Commun. 1999 Aug 27;262(2):411-7. PubMed PMID: 10462489.
217. Schessl J, Taratuto AL, Sewry C, Battini R, Chin SS, Maiti B, Dubrovsky AL,Erro MG, Espada G, Robertella M, Saccoliti M, Olmos P, Bridges LR, Standring P,Hu Y, Zou Y, Swoboda KJ, Scavina M, Goebel HH, Mitchell CA, Flanigan KM, Muntoni F, Bönnemann CG. Clinical, histological and genetic characterization of reducing body myopathy caused by mutations in FHL1. Brain. 2009 Feb;132(Pt 2):452-64. doi:10.1093/brain/awn325. Epub 2009 Jan 29. PubMed PMID: 19181672; PubMed CentralPMCID: PMC2724920.
218. Schmitt JP, Kamisago M, Asahi M, Li GH, Ahmad F, Mende U, Kranias EG,MacLennan DH, Seidman JG, Seidman CE. Dilated cardiomyop athy and heart failurecaused by a mutation in phospholamban. Science. 2003 Feb 28;299(5611):1410-3.PubMed PMID: 12610310.
219. Schott JJ, Benson DW, Basson CT, Pease W, Silberbach GM, Moak JP, Maron BJ,Seidman CE, Seidman JG. Congenital heart disease caused by mutations in thetranscription factor NKX2-5. Science. 1998 Jul 3;281(5373):108-11. PubMed PMID:9651244.
220. Schulz AL, Albrecht B, Arici C, van der Burgt I, Buske A, Gillessen-KaesbachG, Heller R, Horn D, Hübner CA, Korenke GC, König R, Kress W, Krüger G, Meinecke P, Mücke J, Plecko B, Rossier E, Schinzel A, Schulze A, Seemanova E, Seidel H,Spranger S, Tuysuz B, Uhrig S, Wieczorek D, Kutsche K, Zenker M. Mutation andphenotypic spectrum in patients with cardio-facio-cutaneous and Costellosyndrome. Clin Genet. 2008 Jan;73(1):62-70. Epub 2007 Nov 27. PubMed PMID:18042262.
221. Schwartz CE, Tarpey PS, Lubs HA, Verloes A, May MM, Risheg H, Friez MJ,Futreal PA, Edkins S, Teague J, Briault S, Skinner C, Bauer-Carlin A, SimensenRJ, Joseph SM, Jones JR, Gecz J, Stratton MR, Raymond FL, Stevenson RE. Theoriginal Lujan syndrome family has a novel missense mutation (p.N1007S) in theMED12 gene. J Med Genet. 2007 Jul;44(7):472-7. Epub 2007 Mar 16. PubMed PMID:17369503; PubMed Central PMCID: PMC2597996.
222. Schönberger J, Wang L, Shin JT, Kim SD, Depreux FF, Zhu H, Zon L, Pizard A,Kim JB, Macrae CA, Mungall AJ, Seidman JG, Seidman CE. Mutation in thetranscriptional coactivator EYA4 causes dilated cardiomyopathy and sensorineural hearing loss. Nat Genet. 2005 Apr;37(4):418-22. Epub 2005 Feb 27. PubMed PMID:15735644.
223. Scott HS, Bunge S, Gal A, Clarke LA, Morris CP, Hopwood JJ. Molecular geneticsof mucopolysaccharidosis type I: diagnostic, clinical, and biologicalimplications. Hum Mutat. 1995;6(4):288-302. Review. PubMed PMID: 8680403.
224. Scurr I, Wilson L, Lees M, Robertson S, Kirk E, Turner A, Morton J, Kidd A,Shashi V, Stanley C, Berry M, Irvine AD, Goudie D, Turner C, Brewer C, SmithsonS. Cantú syndrome: report of nine new cases and expansion of the clinicalphenotype. Am J Med Genet A. 2011 Mar;155A(3):508-18. doi: 10.1002/ajmg.a.33885. Epub 2011 Feb 22. PubMed PMID: 21344641.
225. Selcen D, Engel AG. Mutations in ZASP define a novel form of musculardystrophy in humans. Ann Neurol. 2005 Feb;57(2):269-76. PubMed PMID: 15668942. 226. Selcen D, Muntoni F, Burton BK, Pegoraro E, Sewry C, Bite AV, Engel AG.Mutation in BAG3 causes severe dominant childhood muscular dystrophy. Ann Neurol.2009 Jan;65(1):83-9.
doi: 10.1002/ana.21553. PubMed PMID: 19085932; PubMedCentral PMCID: PMC2639628. 227. Selga E, Campuzano O, Pinsach-Abuin ML, Pérez-Serra A, Mademont-Soler I, RiuróH, Picó F, Coll M, Iglesias A, Pagans S, Sarquella-Brugada G, Berne P, Benito B, Brugada J, Porres
JM, López Zea M, Castro-Urda V, Fernández-Lozano I, Brugada R. Comprehensive Genetic Characterization of a Spanish Brugada Syndrome Cohort. PLoSOne. 2015 Jul 14;10(7):e0132888. doi: 10.1371/journal.pone.0132888. eCollection2015. PubMed PMID: 26173111; PubMed Central PMCID: PMC4501715.
228. Shackleton S, Lloyd DJ, Jackson SN, Evans R, Niermeijer MF, Singh BM, Schmidt H, Brabant G, Kumar S, Durrington PN, Gregory S, O'Rahilly S, Trembath RC. LMNA, encoding lamin A/C, is mutated in partial lipodystrophy. Nat Genet. 2000Feb;24(2):153-6. PubMed PMID: 10655060.
229. Shen J, Bao Y, Liu HM, Lee P, Leonard JV, Chen YT. Mutations in exon 3 of the glycogen debranching enzyme gene are associated with glycogen storage diseasetype III that is differentially expressed in liver and muscle. J Clin Invest.1996 Jul 15;98(2):352-7. PubMed PMID: 8755644; PubMed Central PMCID: PMC507437.
230. Shinohara M, Saitoh M, Takanashi J, Yamanouchi H, Kubota M, Goto T, Kikuchi M,Shiihara T, Yamanaka G, Mizuguchi M. Carnitine palmitoyl transferase IIpolymorphism is associated with multiple syndromes of acute encephalopathy withvarious infectious diseases. Brain Dev. 2011 Jun;33(6):512-7. doi:10.1016/j.braindev.2010.09.002. Epub 2010 Oct 12. PubMed PMID: 20934285.
231. Sibbing D, Pfeufer A, Perisic T, Mannes AM, Fritz-Wolf K, Unwin S, Sinner MF, Gieger C, Gloeckner CJ, Wichmann HE, Kremmer E, Schäfer Z, Walch A, Hinterseer M,Näbauer M, Kääb S, Kastrati A, Schömig A, Meitinger T, Bornkamm GW, Conrad M, vonBeckerath N. Mutations in the mitochondrial thioredoxin reductase gene TXNRD2cause dilated cardiomyopathy. Eur Heart J. 2011 May;32(9):1121-33. doi:10.1093/eurheartj/ehq507. Epub 2011 Jan 18. PubMed PMID: 21247928.
232. Simard C, Drolet B, Yang P, Kim RB, Roden DM. Polymorphism screening in thecardiac K+ channel gene KCNA5. Clin Pharmacol Ther. 2005 Mar;77(3):138-44. PubMedPMID: 15735608. 233. Smeitink J, van den Heuvel L. Human mitochondrial complex I in health anddisease. Am J Hum Genet. 1999 Jun;64(6):1505-10. Review. PubMed PMID: 10330338;PubMed Central
PMCID: PMC1377894. 234. Splawski I, Shen J, Timothy KW, Lehmann MH, Priori S, Robinson JL, Moss AJ,Schwartz PJ, Towbin JA, Vincent GM, Keating MT. Sp ectrum of mutations in long-QT syndrome genes.
KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation. 2000 Sep5;102(10):1178-85. PubMed PMID: 10973849. 235. Spotila LD, Sereda L, Prockop DJ. Partial isodisomy for maternal chromosome 7 and short stature in an individual with a mutation at the COL1A2 locus. Am J Hum Genet. 1992
Dec;51(6):1396-405. PubMed PMID: 1463018; PubMed Central PMCID:PMC1682915. 236. Stallmeyer B, Zumhagen S, Denjoy I, Duthoit G, Hébert JL, Ferrer X, MaugenreS, Schmitz W, Kirchhefer U, Schulze-Bahr E, Guicheney P, Schulze-Bahr E.Mutational spectrum in the
Ca(2+)--activated cation channel gene TRPM4 inpatients with cardiac conductance disturbances. Hum Mutat. 2012 Jan;33(1):109-17.doi: 10.1002/humu.21599. Epub 2011 Oct 20. PubMed PMID: 21887725.
237. Suzumori N, Kaname T, Muramatsu Y, Yanagi K, Kumagai K, Mizuno S, Naritomi K, Saitoh S, Sugiura-Ogasawara M. Prenatal diagnosis of X-linked recessive Lenzmicrophthalmia syndrome. J Obstet Gynaecol Res. 2013 Nov;39(11):1545-7. doi:10.1111/jog.12081. Epub 2013 Jul 2. PubMed PMID: 23815237.
238. Symoens S, Syx D, Malfait F, Callewaert B, De Backer J, Vanakker O, Coucke P, De Paepe A. Comprehensive molecular analysis demonstrates type V collagenmutations in over 90% of patients with classic EDS and allows to refinediagnostic criteria. Hum Mutat. 2012 Oct;33(10):1485-93. doi: 10.1002/humu.22137.Epub 2012 Jul 5. PubMed PMID: 22696272.
239. Szabo Z, Crepeau MW, Mitchell AL, Stephan MJ, Puntel RA, Yin Loke K, Kirk RC, Urban Z. Aortic aneurysmal disease and cutis laxa caused by defects in theelastin gene. J Med Genet. 2006 Mar;43(3):255-8. Epub 2005 Aug 5. PubMed PMID:16085695; PubMed Central PMCID: PMC2563239.
240. Ta-Shma A, El-lahham N, Edvardson S, Stepensky P, Nir A, Perles Z, Gavri S,Golender J, Yaakobi-Simhayoff N, Shaag A, Rein AJ, Elpeleg O. Conotruncalmalformations and absent thymus due to a deleterious NKX2-6 mutation. J MedGenet. 2014 Apr;51(4):268-70. doi: 10.1136/jmedgenet-2013-102100. Epub 2014 Jan13. PubMed PMID: 24421281.
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241. Tahara T, Kraus JP, Rosenberg LE. An unusual insertion/deletion in the geneencoding the beta-subunit of propionyl-CoA carboxylase is a frequent mutation in Caucasian propionic acidemia. Proc Natl Acad Sci U S A. 1990 Feb;87(4):1372-6.PubMed PMID: 2154743; PubMed Central PMCID: PMC53477.
242. Tajsharghi H, Thornell LE, Lindberg C, Lindvall B, Henriksson KG, Oldfors A.Myosin storage myopathy associated with a heterozygous missense mutation in MYH7.Ann Neurol. 2003 Oct;54(4):494-500. PubMed PMID: 14520662.
243. Tan HL, Glen E, Töpf A, Hall D, O'Sullivan JJ, Sneddon L, Wren C, Avery P,Lewis RJ, ten Dijke P, Arthur HM, Goodship JA, Keavney BD. Nonsynonymous variantsin the SMAD6 gene predispose to congenital cardiovascular malformation. HumMutat. 2012 Apr;33(4):720-7. doi: 10.1002/humu.22030. Epub 2012 Feb 14. PubMedPMID: 22275001; PubMed Central PMCID: PMC3492913.
244. Taroni F, Verderio E, Fiorucci S, Cavadini P, Finocchiaro G, Uziel G, LamanteaE, Gellera C, DiDonato S. Molecular characterization of inherited carnitinepalmitoyltransferase II deficiency. Proc Natl Acad Sci U S A. 1992 Sep15;89(18):8429-33. PubMed PMID: 1528846; PubMed Central PMCID: PMC49933.
245. Tartaglia M, Mehler EL, Goldberg R, Zampino G, Brunner HG, Kremer H, van derBurgt I, Crosby AH, Ion A, Jeffery S, Kalidas K, Patton MA, Kucherlapati RS, GelbBD. Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, causeNoonan syndrome. Nat Genet. 2001 Dec;29(4):465-8. Erratum in: Nat Genet 2002Jan;30(1):123. Nat Genet 2001 Dec;29(4):491. PubMed PMID: 11704759.
246. Tateyama M, Aoki M, Nishino I, Hayashi YK, Sekiguchi S, Shiga Y, Takahashi T, Onodera Y, Haginoya K, Kobayashi K, Iinuma K, Nonaka I, Arahata K, Itoyama Y.Mutation in the caveolin-3 gene causes a peculiar form of distal myopathy.Neurology. 2002 Jan 22;58(2):323-5. Erratum in: Neurology 2002 Mar 12;58(5):839. Itoyoma Y [corrected to Itoyama Y]. PubMed PMID: 11805270.
247. Taylor MR, Slavov D, Gajewski A, Vlcek S, Ku L, Fain PR, Carniel E, Di LenardaA, Sinagra G, Boucek MM, Cavanaugh J, Graw SL, Ruegg P, Feiger J, Zhu X, FergusonDA, Bristow MR, Gotzmann J, Foisner R, Mestroni L; Familial CardiomyopathyRegistry Research Group. Thymopoietin (lamina-associated polypeptide 2) genemutation associated with dilated cardiomyopathy. Hum Mutat. 2005Dec;26(6):566-74. PubMed PMID: 16247757.
248. Taşkesen M, Collin GB, Evsikov AV, Güzel A, Özgül RK, Marshall JD, Naggert JK.Novel Alu retrotransposon insertion leading to Alström syndrome. Hum Genet. 2012 Mar;131(3):407- 13. doi: 10.1007/s00439-011-1083-9. Epub 2011 Aug 30. PubMed PMID:21877133; PubMed Central PMCID: PMC3264847.
249. Theis JL, Bos JM, Bartleson VB, Will ML, Binder J, Vatta M, Towbin JA, GershBJ, Ommen SR, Ackerman MJ. Echocardiographic-determined septal morphology inZ-disc hypertrophic cardiomyopathy. Biochem Biophys Res Commun. 2006 Dec29;351(4):896-902. Epub 2006 Nov 9. PubMed PMID: 17097056.
250. Theis JL, Sharpe KM, Matsumoto ME, Chai HS, Nair AA, Theis JD, de Andrade M,Wieben ED, Michels VV, Olson TM. Homozygosity map ping and exome sequencing revealGATAD1 mutation in autosomal recessive dilated cardiomyopathy. Circ CardiovascGenet. 2011 Dec;4(6):585-94. doi: 10.1161/CIRCGENETICS.111.961052. Epub 2011 Sep 30. PubMed PMID: 21965549; PubMed Central PMCID: PMC3248690.
251. Thomson JR, Machado RD, Pauciulo MW, Morgan NV, Humbert M, Elliott GC, Ward K,Yacoub M, Mikhail G, Rogers P, Newman J, Wheeler L, Higenbottam T, Gibbs JS, EganJ, Crozier A, Peacock A, Allcock R, Corris P, Loyd JE, Trembath RC, Nichols WC.Sporadic primary pulmonary hypertension is associated with germline mutations of the gene encoding BMPR-II, a receptor member of the TGF-beta family. J Med Genet.2000 Oct;37(10):741-5. PubMed PMID: 11015450; PubMed Central PMCID: PMC1757155.
252. Timal S, Hoischen A, Lehle L, Adamowicz M, Huijben K, Sykut-Cegielska J,Paprocka J, Jamroz E, van Spronsen FJ, Körner C, Gilissen C, Rodenburg RJ, EidhofI, Van den Heuvel L, Thiel C, Wevers RA, Morava E, Veltman J, Lefeber DJ. Geneidentification in the congenital disorders of glycosylation type I by whole-exomesequencing. Hum Mol Genet. 2012 Oct 1;21(19):4151-61. doi: 10.1093/hmg/dds123.Epub 2012 Apr 5. PubMed PMID: 22492991.
253. Tsubata S, Bowles KR, Vatta M, Zintz C, Titus J, Muhonen L, Bowles NE, Towbin JA. Mutations in the human delta-sarcoglycan gene in familial and sporadicdilated cardiomyopathy. J Clin Invest. 2000 Sep;106(5):655-62. PubMed PMID:10974018; PubMed Central PMCID: PMC381284.
254. Tsuji S, Choudary PV, Martin BM, Stubblefield BK, Mayor JA, Barranger JA,Ginns EI. A mutation in the human glucocerebrosidase gene in neuronopathicGaucher's disease. N Engl J Med. 1987 Mar 5;316(10):570-5. PubMed PMID: 2880291.
255. Ueda K, Hirano Y, Higashiuesato Y, Aizawa Y, Hayashi T, Inagaki N, Tana T,Ohya Y, Takishita S, Muratani H, Hiraoka M, Kimura A. Role of HCN4 channel inpreventing ventricular arrhythmia. J Hum Genet. 2009 Feb;54(2):115-21. doi:10.1038/jhg.2008.16. Epub 2009 Jan 23. PubMed PMID: 19165230.
256. Valdés-Mas R, Gutiérrez-Fernández A, Gómez J, Coto E, Astudillo A, Puente DA, Reguero JR, Álvarez V, Morís C, León D, Martín M, Puente XS, López-Otín C.Mutations in filamin C cause a new form of familial hypertrophic cardiomyopathy. Nat Commun. 2014 Oct 29;5:5326. doi: 10.1038/ncomms6326. PubMed PMID: 25351925.
257. Valnot I, Osmond S, Gigarel N, Mehaye B, Amiel J, Cormier-Daire V, Munnich A, Bonnefont JP, Rustin P, Rötig A. Mutations of the SCO1 gene in mitochondrialcytochrome c oxidase deficiency with neonatal-onset hepatic failure andencephalopathy. Am J Hum Genet. 2000 Nov;67(5):1104-9. Epub 2000 Sep 28. PubMedPMID: 11013136; PubMed Central PMCID: PMC1288552.
258. Van Norstrand DW, Valdivia CR, Tester DJ, Ueda K, London B, Makielski JC,Ackerman MJ. Molecular and functional characterization of novelglycerol-3-phosphate dehydrogenase 1 like gene (GPD1-L) mutations in suddeninfant death syndrome. Circulation. 2007 Nov 13;116(20):2253-9. Epub 2007 Oct 29.PubMed PMID: 17967976; PubMed Central PMCID: PMC3332545.
259. Vasko V, Ferrand M, Di Cristofaro J, Carayon P, Henry JF, de Micco C. Specificpattern of RAS oncogene mutations in follicular thyroid tumors. J Clin EndocrinolMetab. 2003 Jun;88(6):2745-52. PubMed PMID: 12788883.
260. Vatta M, Ackerman MJ, Ye B, Makielski JC, Ughanze EE, Taylor EW, Tester DJ,Balijepalli RC, Foell JD, Li Z, Kamp TJ, Towbin JA. Mutant caveolin-3 inducespersistent late sodium current and is associated with long-QT syndrome.Circulation. 2006 Nov 14;114(20):2104-12. Epub 2006 Oct 23. PubMed PMID:17060380.
261. Vatta M, Mohapatra B, Jimenez S, Sanchez X, Faulkner G, Perles Z, Sinagra G,Lin JH, Vu TM, Zhou Q, Bowles KR, Di Lenarda A, Schimmenti L, Fox M, Chrisco MA, Murphy RT, McKenna W, Elliott P, Bowles NE, Chen J, Valle G, Towbin JA. Mutationsin Cypher/ZASP in patients with dilated cardiomyopathy and left ventricularnon-compaction. J Am Coll Cardiol. 2003 Dec 3;42(11):2014-27. PubMed PMID:14662268.
262. Vervoort R, Islam MR, Sly WS, Zabot MT, Kleijer WJ, Chabas A, Fensom A, Young EP, Liebaers I, Lissens W. Molecular analysis of patients with beta-glucuronidasedeficiency presenting as hydrops fetalis or as early mucopolysaccharidosis VII.Am J Hum Genet. 1996 Mar;58(3):457-71. PubMed PMID: 8644704; PubMed CentralPMCID: PMC1914559.
263. Vicart P, Caron A, Guicheney P, Li Z, Prévost MC, Faure A, Chateau D, ChaponF, Tomé F, Dupret JM, Paulin D, Fardeau M. A missense mutation in thealphaB-crystallin chaperone gene causes a desmin-related myopathy. Nat Genet.1998 Sep;20(1):92-5. PubMed PMID: 9731540.
264. Villanueva MP, Aiyer AR, Muller S, Pletcher MT, Liu X, Emanuel B, SrivastavaD, Reeves RH. Genetic and comparative mapping of genes dysregulated in mousehearts lacking the Hand2 transcription factor gene. Genomics. 2002Dec;80(6):593-600. PubMed PMID: 12504851.
265. Vorgerd M, van der Ven PF, Bruchertseifer V, Löwe T, Kley RA, Schröder R,Lochmüller H, Himmel M, Koehler K, Fürst DO, Huebner A. A mutation in thedimerization domain of filamin c causes a novel type of autosomal dominantmyofibrillar myopathy. Am J Hum Genet. 2005 Aug;77(2):297-304. Epub 2005 May 31. PubMed PMID: 15929027; PubMed Central PMCID: PMC1224531.
266. Wallace RH, Wang DW, Singh R, Scheffer IE, George AL Jr, Phillips HA, Saar K, Reis A, Johnson EW, Sutherland GR, Berkovic SF, Mulley JC. Febrile seizures andgeneralized epilepsy associated with a mutation in the Na+-channel beta1 subunit gene SCN1B. Nat Genet. 1998 Aug;19(4):366-70. PubMed PMID: 9697698.
267. Walter MC, Reilich P, Huebner A, Fischer D, Schröder R, Vorgerd M, Kress W,Born C, Schoser BG, Krause KH, Klutzny U, Bulst S, Frey JR, Lochmüller H.Scapuloperoneal syndrome type Kaeser and a wide phenotypic spectrum ofadult-onset, dominant myopathies are associated with the desmin mutation R350P.Brain. 2007 Jun;130(Pt 6):1485-96. Epub 2007 Apr 17. PubMed PMID: 17439987.
268. Wang B, Yan J, Mi R, Zhou S, Xie X, Wang J, Ma X. Forkhead box H1 (FOXH1)sequence variants in ventricular septal defect. Int J Cardiol. 2010 Nov5;145(1):83-5. doi: 10.1016/j.ijcard.2009.05.030. Epub 2009 Jun 13. PubMed PMID: 19525021.
269. Wang H, Li Z, Wang J, Sun K, Cui Q, Song L, Zou Y, Wang X, Liu X, Hui R, FanY. Mutations in NEXN, a Z-disc gene, are associated with hypertrophiccardiomyopathy. Am J Hum Genet. 2010 Nov 12;87(5):687-93. doi:10.1016/j.ajhg.2010.10.002. Epub 2010 Oct 21. PubMed PMID: 20970104; PubMedCentral PMCID: PMC2978958.
270. Wang L, Guo DC, Cao J, Gong L, Kamm KE, Regalado E, Li L, Shete S, He WQ, Zhu MS, Offermanns S, Gilchrist D, Elefteriades J, Stull JT, Milewicz DM. Mutationsin myosin light chain kinase cause familial aortic dissections. Am J Hum Genet.2010 Nov 12;87(5):701-7. doi: 10.1016/j.ajhg.2010.10.006. Epub 2010 Nov 4.Erratum in: Am J Hum Genet. 2011 Apr 8;88(4):516. PubMed PMID: 21055718; PubMedCentral PMCID: PMC2978973.
271. Wang P, Yang Q, Wu X, Yang Y, Shi L, Wang C, Wu G, Xia Y, Yang B, Zhang R, Xu C, Cheng X, Li S, Zhao Y, Fu F, Liao Y, Fang F, Chen Q, Tu X, Wang QK. Functionaldominant- negative mutation of sodium channel subunit gene SCN3B associated withatrial fibrillation in a Chinese GeneID population. Biochem Biophys Res Commun.2010 Jul 16;398(1):98- 104. doi: 10.1016/j.bbrc.2010.06.042. Epub 2010 Jun 15.PubMed PMID: 20558140; PubMed Central PMCID: PMC3132081.
272. Wang Q, Curran ME, Splawski I, Burn TC, Millholland JM, VanRaay TJ, Shen J,Timothy KW, Vincent GM, de Jager T, Schwartz PJ, Toubin JA, Moss AJ, Atkinson DL,Landes GM, Connors TD, Keating MT. Positional cloning of a novel potassiumchannel gene: KVLQT1 mutations cause cardiac arrhythmias. Nat Genet. 1996Jan;12(1):17-23. PubMed PMID: 8528244.
273. Wang Q, Shen J, Splawski I, Atkinson D, Li Z, Robinson JL, Moss AJ, Towbin JA,Keating MT. SCN5A mutations associated with an inherited cardiac arrhythmia, longQT syndrome. Cell. 1995 Mar 10;80(5):805-11. PubMed PMID: 7889574.
274. Watanabe H, Darbar D, Kaiser DW, Jiramongkolchai K, Chopra S, Donahue BS,Kannankeril PJ, Roden DM. Mutations in sodium channel β1- and β2-subunitsassociated with atrial fibrillation. Circ Arrhythm Electrophysiol. 2009Jun;2(3):268-75. doi: 10.1161/CIRCEP.108.779181. Epub 2009 Mar 6. PubMed PMID:19808477; PubMed Central PMCID: PMC2727725.
275. Wehner LE, Folz BJ, Argyriou L, Twelkemeyer S, Teske U, Geisthoff UW, WernerJA, Engel W, Nayernia K. Mutation analysis in hereditary haemorrhagictelangiectasia in Germany reveals 11 novel ENG and 12 novel ACVRL1/ALK1mutations. Clin Genet. 2006 Mar;69(3):239-45. PubMed PMID: 16542389.
276. Wightman PJ, Santer R, Ribes A, Dougherty F, McGill N, Thorburn DR,FitzPatrick DR. MLYCD mutation analysis: evidence for prot ein mistargeting as acause of MLYCD deficiency. Hum Mutat. 2003 Oct;22(4):288-300. PubMed PMID:12955715.
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277. Windpassinger C, Schoser B, Straub V, Hochmeister S, Noor A, Lohberger B,Farra N, Petek E, Schwarzbraun T, Ofner L, Löscher WN, Wagner K, Lochmüller H,Vincent JB, Quasthoff S. An X-linked myopathy with postural muscle atrophy andgeneralized hypertrophy, termed XMPMA, is caused by mutations in FHL1. Am J HumGenet. 2008 Jan;82(1):88-99. doi: 10.1016/j.ajhg.2007.09.004. PubMed PMID:18179888; PubMed Central PMCID: PMC2253986.
278. Wooderchak-Donahue WL, McDonald J, O'Fallon B, Upton PD, Li W, Roman BL, YoungS, Plant P, Fülöp GT, Langa C, Morrell NW, Botella LM, Bernabeu C, Stevenson DA, Runo JR, Bayrak-Toydemir P. BMP9 mutations cause a vascular-anomaly syndrome withphenotypic overlap with hereditary hemorrhagic telangiectasia. Am J Hum Genet.2013 Sep 5;93(3):530- 7. doi: 10.1016/j.ajhg.2013.07.004. Epub 2013 Aug 22. PubMedPMID: 23972370; PubMed Central PMCID: PMC3769931.
279. Wu G, Ai T, Kim JJ, Mohapatra B, Xi Y, Li Z, Abbasi S, Purevjav E, Samani K,Ackerman MJ, Qi M, Moss AJ, Shimizu W, Towbin JA, Cheng J, Vatta M.alpha-1-syntrophin mutation and the long-QT syndrome: a disease of sodium channeldisruption. Circ Arrhythm Electrophysiol. 2008 Aug;1(3):193-201. doi:10.1161/CIRCEP.108.769224. PubMed PMID: 19684871; PubMed Central PMCID:PMC2726717.
280. Yagi H, Furutani Y, Hamada H, Sasaki T, Asakawa S, Minoshima S, Ichida F, Joo K, Kimura M, Imamura S, Kamatani N, Momma K, Takao A, Nakazawa M, Shimizu N,Matsuoka R. Role of TBX1 in human del22q11.2 syndrome. Lancet. 2003 Oct25;362(9393):1366-73. PubMed PMID: 14585638.
281. Yamamoto GL, Aguena M, Gos M, Hung C, Pilch J, Fahiminiya S, Abramowicz A,Cristian I, Buscarilli M, Naslavsky MS, Malaquias AC, Zatz M, Bodamer O, MajewskiJ, Jorge AA, Pereira AC, Kim CA, Passos-Bueno MR, Bertola DR. Rare variants inSOS2 and LZTR1 are associated with Noonan syndrome. J Med Genet. 2015Jun;52(6):413-21. doi: 10.1136/jmedgenet-2015-103018. Epub 2015 Mar 20. PubMedPMID: 25795793
282. Yamamoto GL, Aguena M, Gos M, Hung C, Pilch J, Fahiminiya S, Abramowicz A,Cristian I, Buscarilli M, Naslavsky MS, Malaquias AC, Zatz M, Bodamer O, MajewskiJ, Jorge AA, Pereira AC, Kim CA, Passos-Bueno MR, Bertola DR. Rare variants inSOS2 and LZTR1 are associated with Noonan syndrome. J Med Genet. 2015Jun;52(6):413-21. doi: 10.1136/jmedgenet-2015-103018. Epub 2015 Mar 20. PubMedPMID: 25795793.
283. Yang YQ, Zhang XL, Wang XH, Tan HW, Shi HF, Jiang WF, Fang WY, Liu X.Connexin40 nonsense mutation in familial atrial fibrillation. Int J Mol Med. 2010Oct;26(4):605-10. PubMed PMID: 20818502.
284. Yeowell HN, Walker LC. Mutations in the lysyl hydroxylase 1 gene that resultin enzyme deficiency and the clinical phenotype of Ehlers-Danlos syndrome typeVI. Mol Genet Metab. 2000 Sep-Oct;71(1-2):212-24. Review. PubMed PMID: 11001813.
285. Zampieri S, Filocamo M, Buratti E, Stroppiano M, Vlahovicek K, Rosso N,Bignulin E, Regis S, Carnevale F, Bembi B, Dardis A. Molecular and functionalanalysis of the HEXB gene in Italian patients affected with Sandhoff disease:identification of six novel alleles. Neurogenetics. 2009 Feb;10(1):49-58. doi:10.1007/s10048-008-0145-1. Epub 2008 Aug 29. PubMed PMID: 18758829.
286. Zhang L, Hu A, Yuan H, Cui L, Miao G, Yang X, Wang L, Liu J, Liu X, Wang S,Zhang Z, Liu L, Zhao R, Shen Y. A missense mutatio n in the CHRM2 gene isassociated with familial dilated cardiomyopathy. Circ Res. 2008 Jun6;102(11):1426-32. doi: 10.1161/CIRCRESAHA.107.167783. Epub 2008 May 1. PubMedPMID: 18451336.
287. Zhou YM, Dai XY, Qiu XB, Yuan F, Li RG, Xu YJ, Qu XK, Huang RT, Xue S, YangYQ. HAND1 loss-of-function mutation associated with familial dilatedcardiomyopathy. Clin Chem Lab Med. 2016 Jul 1;54(7):1161-7. doi:10.1515/cclm-2015-0766. PubMed PMID: 26581070.
288. Zhu L, Vranckx R, Khau Van Kien P, Lalande A, Boisset N, Mathieu F, Wegman M, Glancy L, Gasc JM, Brunotte F, Bruneval P, Wolf JE, Michel JB, Jeunemaitre X.Mutations in myosin heavy chain 11 cause a syndrome associating thoracic aorticaneurysm/aortic dissection and patent ductus arteriosus. Nat Genet. 2006Mar;38(3):343-9. Epub 2006 Jan 29. PubMed PMID: 16444274.
289. di Barletta MR, Viatchenko-Karpinski S, Nori A, Memmi M, Terentyev D, Turcato F, Valle G, Rizzi N, Napolitano C, Gyorke S, Volpe P, Priori SG. Clinicalphenotype and functional characterization of CASQ2 mutations associated withcatecholaminergic polymorphic ventricular tachycardia. Circulation. 2006 Sep5;114(10):1012-9. Epub 2006 Aug 14. PubMed PMID: 16908766.
290. van Engelen BG, Muchir A, Hutchison CJ, van der Kooi AJ, Bonne G, Lammens M.The lethal phenotype of a homozygous nonsense mut ation in the lamin A/C gene.Neurology. 2005 Jan 25;64(2):374-6. PubMed PMID: 15668447.
291. van Hengel J, Calore M, Bauce B, Dazzo E, Mazzotti E, De Bortoli M, LorenzonA, Li Mura IE, Beffagna G, Rigato I, Vleeschouwers M, Tyberghein K, Hulpiau P,van Hamme E, Zaglia T, Corrado D, Basso C, Thiene G, Daliento L, Nava A, van Roy F, Rampazzo A. Mutations in the area composita protein αT-catenin are associated with arrhythmogenic right ventricular cardiomyopathy. Eur Heart J. 2013Jan;34(3):201-10. doi: 10.1093/eurheartj/ehs373. Epub 2012 Nov 7. PubMed PMID:23136403.
292. van de Laar IM, van der Linde D, Oei EH, Bos PK, Bessems JH, Bierma-ZeinstraSM, van Meer BL, Pals G, Oldenburg RA, Bekkers JA, Moelker A, de Graaf BM, MatyasG, Frohn- Mulder IM, Timmermans J, Hilhorst-Hofstee Y, Cobben JM, Bruggenwirth HT,van Laer L, Loeys B, De Backer J, Coucke PJ, Dietz HC, Willems PJ, Oostra BA, De Paepe A, Roos- Hesselink JW, Bertoli-Avella AM, Wessels MW. Phenotypic spectrum ofthe SMAD3-related aneurysms-osteoarthritis syndrome. J Med Genet. 2012Jan;49(1):47-57. doi: 10.1136/jmedgenet-2011-100382. PubMed PMID: 22167769.
293. van den Bosch BJ, Gerards M, Sluiter W, Stegmann AP, Jongen EL, HellebrekersDM, Oegema R, Lambrichs EH, Prokisch H, Danhauser K, Schoonderwoerd K, de Coo IF,Smeets HJ. Defective NDUFA9 as a novel cause of neonatally fatal complex Idisease. J Med Genet. 2012 Jan;49(1):10-5. doi: 10.1136/jmedgenet-2011-100466.Epub 2011 Nov 23. PubMed PMID: 22114105..
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Disclaimer
This test was developed and its performance characteristics were determined by Mount Sinai Genomics, Inc. DBA Sema4 and was considered acceptable for patient testing. It has not been cleared or approved by the FDA. The FDA has determined that such clearance or approval is not necessary. This type of mutation analysis generally provides highly accurate genotype information for microdeletions and microduplications. Despite this level of accuracy, it should be kept in mind that there are many potential sources of diagnostic error, including misidentification of samples, rare polymorphisms, or other rare genetic variants that interfere with analysis. In addition, families should understand the limitations of the testing and that rare diagnostic errors may occur for the reasons described.