Hypertrophic Cardiomyopathy (HCM) Panel (20 Genes) Test Details
Hypertrophic cardiomyopathy (HCM) is characterized by unexplained left ventricular hypertrophy (LVH) in a non-dilated ventricle. It is the most common monogenic cardiac disorder and is estimated to affect approximately 1/500 with approximately half having a family history. HCM is typically inherited in an autosomal dominant pattern with incomplete penetrance and variable expressivity. Variants in genes involved in storage diseases typically causing systemic disease, but may also result in predominant cardiac manifestations that can mimic HCM. For additional information about HCM, please visit GeneReviews.
Available Cardiomyopathy Panel Tests
Current tests for HCM
- HCM Panel (20 genes)
- For cases with a clear diagnosis of HCM
- Pan Cardiomyopathy Panel (62 genes)
- For cases with an unclear diagnosis
- For diseases where the genetic contribution is incompletely characterized (e.g. LVNC, RCM)
- For comprehensive testing
Read More for expanded gene table.Read More...
|ACTC1||Actin, Alpha, Cardiac Muscle||102540||15q14|
|CSRP3||Cysteine- And Glycine-Rich Protein 3||600824||11p15.1|
|LAMP2||Lysosome-Associated Membrane Protein 2||309060||Xq24|
|MYBPC3||Myosin-Binding Protein C, Cardiac||600958||11p11.2|
|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|
|PRKAG2||Protein Kinase, AMP-Activated, Noncatalytic, Gamma-2||602743||7q36.1|
|PTPN11||Protein-Tyrosine Phosphatase, Nonreceptor-Type, 11||176876||12q24.13|
|RAF1||V-RAF-1 Murine Leukemia Viral Oncogene Homolog 1||164760||3p25.2|
|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 HCM Panel should be ordered for individuals with a clear diagnosis of HCM. This panel will provide comprehensive coverage of the implicated genes and minimize 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 genes 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.
The detection rate of the HCM Panel (18 Genes) is approximately 32% for all cases HCM, but increases to ~50% for those with a family history of HCM.