Dilated Cardiomyopathy (DCM)/Arrhythmogenic Cardiomyopathy Panel (53 Genes) Test Details
Dilated cardiomyopathy (DCM) is characterized by ventricular chamber enlargement and systolic dysfunction with normal left ventricular wall thickness. It is estimated to affect approximately 1/2,500 with ~20-35% having a family history. DCM is typically inherited in an autosomal dominant pattern with incomplete penetrance and variable expressivity. Variants in some genes can cause additional abnormalities in conjunction with DCM, including conduction system disease and skeletal myopathy. For additional information about DCM, please visit GeneReviews.Read More...
Arrhythmogenic cardiomyopathies (AC) encompass a spectrum of diseases, the classic form of which is arrhythmogenic right ventricular cardiomyopathy (ARVC), though recognition of phenotypic variability recently prompted adoption of a broader term. ARVC is characterized by replacement of myocytes by fatty or fibrofatty tissue, mainly in the right ventricle, with broad manifestations including ventricular tachyarrhythmias and sudden death, and is estimated to affect approximately 1/2,000 to 1/5,000 with 30-50% having a family history. The spectrum of AC now includes the wider clinical spectrum for ARVC, left-dominant AC (LDAC) and bi-ventricular forms that may be misdiagnosed as DCM or myocarditis, as well as syndromic forms (Naxos and Carvajal syndromes). Arrhythmogenic cardiomyopathies are typically inherited in an autosomal dominant pattern with incomplete penetrance and variable expressivity, though recessive inheritance is also reported. For additional information about arrhythmogenic cardiomyopathies, please refer to: Sen-Chowdhry 2010, PubMed ID 20059337; Saffitz 2011, PubMed ID 21986778; Rizzo 2012, PubMed ID 22476658; and ElMaghawry 2013, PubMed ID 24689002.
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is typically characterized by exercise induced syncope due to ventricular tachycardia in individuals without structural heart disease. It is estimated to affect approximately 1/10,000 and the majority of cases are inherited in an autosomal dominant pattern, though autosomal recessive inheritance has also been described. For additional information about CPVT, please visit GeneReviews.Less
Available Cardiomyopathy Panel Tests
DCM/Arrhythmogenic Cardiomyopathy Panel (53 genes)
- For cases with DCM, arrhythmogenic cardiomyopathies, or CPVT
- Pan Cardiomyopathy Panel (62 genes)
- For cases with an unclear diagnosis
- For diagnoses where the genetic contribution is incompletely characterized (e.g. LVNC, RCM)
- For comprehensive testing
Read More for expanded gene table.Read More...
|ABCC9||ATP-Binding Cassette, Subfamily C, Member 9||601439||12p12.1|
|ACTC1||Actin, Alpha, Cardiac Muscle||102540||15q14|
|BAG3||BCL2-Associated Athanogene 3||603883||10q25.2-q26.2|
|CHRM2||Cholinergic Receptor, Muscarinic, 2||118493||7q33|
|CSRP3||Cysteine- And Glycine-Rich Protein 3||600824||11p15.1|
|GATAD1||Gata Zinc Finger Domain-Containing Protein 1||614518||7q21-q22|
|LAMP2||Lysosome-Associated Membrane Protein 2||309060||Xq24|
|LDB3||Lim Domain-Binding 3||605906||10q22.3-q23.2|
|MURC||Muscle Related Coiled-Coil Protein||n/a||9q31.1|
|MYBPC3||Myosin-Binding Protein C, Cardiac||600958||11p11.2|
|MYH6||Myosin, Heavy Chain 6, Cardiac Muscle, Alpha||160710||14q12|
|MYH7||Myosin, Heavy Chain 7, Cardiac Muscle, Beta||160760||14q12|
|MYL2||Myosin, Light Chain 2, Regulatory, Cardiac, Slow||160781||12q24.11|
|MYL3||Myosin, Light Chain 3, Alkali, Ventricular, Skeletal, Slow||160790||3p21.3-p21.2|
|NEXN||Nexilin (F Actin Binding Protein)||613121||1p31.1|
|PRDM16||PR Domain-Containing Protein 16||605557||1p36.32|
|PRKAG2||Protein Kinase, AMP-Activated, Noncatalytic, Gamma-2||602743||7q36.1|
|PTPN11||Protein-Tyrosine Phosphatase, Nonreceptor-Type 11||176876||12q24.1|
|RAF1||V-RAF-1 Murine Leukemia Viral Oncogne Homolog 1||164760||3p25|
|RBM20||RNA-Binding Motif Protein 20||613171||10q25.2|
|RYR2||Ryanodine Receptor 2 (Cardiac)||180902||1q43|
|SCN5A||Sodium Channel, Voltage-Gated, Type V, Alpha Subunit||600163||3p21|
|SGCD||Sarcoglycan, Delta (35Kda Dystrophin-Associated Glycoprotein)||601411||5q33-q34|
|TMEM43||Transmembrane Protein 43||612048||3p25.1|
|TNNC1||Troponin C Type 1 (Slow)||191040||3p21.1|
|TNNI3||Troponin I Type 3 (Cardiac)||191044||19q13.4|
|TNNT2||Troponin T Type 2 (Cardiac)||191045||1q32|
|TPM1||Tropomyosin 1 (Alpha)||191010||15q22.1|
The DCM/Arrhythmogenic Cardiomyopathy Panel should be ordered for patients with a diagnosis of DCM, arrhythmogenic cardiomyopathy (including ARVC), or CPVT. This panel will provide comprehensive coverage of the implicated genes and reduce the incidence of variants of unknown significance compared with the Pan Cardiomyopathy panel.
The Pan Cardiomyopathy Panel is best suited for individuals who have already exhausted current testing options or those whose clinical diagnosis is not yet clear and offers comprehensive testing for gene for all forms of cardiomyopathy. However, interpretation of a novel variant may be more difficult if it is found in a gene that is not (yet) known to cause the individual’s cardiomyopathy and, in many individuals, results in a higher number of variants of uncertain significance compared to the respective subpanel.
This test is performed by next-generation sequencing, using Agilent SureSelect capture, followed by sequencing of the coding regions and splice sites, using Illumina sequencing technologies. Variant calls are generated, using the Burrows-Wheeler Aligner, followed by Genomic Analysis Tool Kit (GATK) analysis. Detection of copy number variants (CNVs) encompassing 1 or more exons is performed, using VisCap™ analysis. Sanger sequencing is used to fill in regions with insufficient coverage. All clinically significant variants are confirmed by Sanger sequencing or an alternate assay. Variants classified as likely benign or benign are not confirmed. This test does not detect variants in non-coding regions, aside from the splice junctions, that could affect gene expression, and a few exons have been excluded, due to technical difficulties. CNV analysis is only performed when data meets necessary quality standards and may not be available for all cases.
Analytical and Clinical Sensitivity
This test is 100.00% sensitive (525/525 variants tested; 95% CI = 99.27-100.00% ) to detect variants changing a single base and 100.00% sensitive to detect insertion/deletions 1-21 bp in size (17/17 variants tested; 95% CI = 81.57-100.00%). Regions with high sequence homology are included in this test if a unique Sanger sequencing assay can be designed to rule out false positive calls. Analytical sensitivity in these regions may be reduced.
Up to 37% of cases of DCM have a clinically relevant variant identified and does not appear to differ in individuals with a family history (Pugh 2014). The detection rate is approximately 30-50% for ARVC (Cox 2011, Fressart 2010) and ~50-55% for CPVT (GeneReviews).