Hypertrophic Cardiomyopathy (HCM) Panel

  • bpg-method PLUS
  • bpg-method SEQ
  • bpg-method DEL/DUP

Test code: CA1901

The Blueprint Genetics Hypertrophic Cardiomyopathy (HCM) Panel is a 19-gene test for genetic diagnostics of patients with clinical suspicion of cardiomagaly, hypertrophic cardiomyopathy (HCM), obstructive HCM or restrictive cardiomyopathy (RCM).

Majority of hypertrophic cardiomyopathy (HCM) is inherited in an autosomal dominant manner. In rare cases HCM can be inherited in an X-linked pattern. Establishing genetic diagnosis Confirms or modifies the clinical diagnosis. Without genetic diagnosis it is often impossible to differentiate a sarcomer disease from Fabry disease, glycogen storage diseases or certain rasopathies. By defining the etiology of HCM it enables disease specific estimates on prognostics and treatment paths. Genetic diagnosis enables risk stratification among family members and rationalizes the future follow-ups of relatives. Genetic diagnosis can decrease the costs of screening family members at risk. Hypertrophic Cardiomyopathy (HCM) Panel can be used also for patients with restrictive cardiomyopathy (RCM). Hypertrophic Cardiomyopathy (HCM) Panel is part of the Cardiomyopathy Panel and Comprehensive Cardiology Panel.

Ackerman, M.J. et al. HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies: this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA). Europace 2011, 13(8) , 1077–1109.

Ando, Y. et al., 2013. Guideline of transthyretin-related hereditary amyloidosis for clinicians. Orphanet J Rare Dis, 8, p.31.

Ashley, E.A. et al., 2012. Genetics and cardiovascular disease: a policy statement from the American Heart Association. Circulation, 126(1), pp.142–157.

Charron, P. et al. Genetic counselling and testing in cardiomyopathies: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J 2010, (22), 2715–2726.

Dubrey, S.W. et al. 2011. Amyloid diseases of the heart: assessment, diagnosis, and referral. Heart, 97(1), pp.75–84.

Gersh, B.J. et al., 2011. 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation, 124(24), pp.2761–2796.

Gollob, M.H. et al., 2011. Recommendations for the use of genetic testing in the clinical evaluation of inherited cardiac arrhythmias associated with sudden cardiac death: Canadian Cardiovascular Society/Canadian Heart Rhythm Society joint position paper. Can J Card, 27(2), pp.232–245.

Hershberger, R.E. et al., 2009. Genetic evaluation of cardiomyopathy–a Heart Failure Society of America practice guideline. J Card Failure, 15(2), pp.83–97.

Ingles, J. et al. A cost-effectiveness model of genetic testing for the evaluation of families with hypertrophic cardiomyopathy. Heart 2012, 98(8), 625–630.

Ingles, J. et al., 2013. Clinical predictors of genetic testing outcomes in hypertrophic cardiomyopathy. Genetics in Medicine, 15(12), pp.972–977.

Katzin, L.W. & Amato, A.A., 2008. Pompe disease: a review of the current diagnosis and treatment recommendations in the era of enzyme replacement therapy. J Clin Neuromusc Dis, 9(4), pp.421–431.

Maron, B.J., 1997. Hypertrophic cardiomyopathy. Lancet, 350(9071), pp.127–133.

Maron, B.J. & Maron, M.S., 2013. Hypertrophic cardiomyopathy. Lancet, 381(9862), pp.242–255.

Maron, B.J. et al. Contemporary Definitions and Classification of the Cardiomyopathies: An American Heart Association Scientific Statement From the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation 2006, 113(14), 1807–1816.

Rauen, K.A., 2013. The RASopathies. Annu Rev Genomics Hum Genet, 14, pp.355–369.

Richards S et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015 Mar 5, in press.

About Hypertrophic Cardiomyopathy (HCM)

Hypertrophic cardiomyopathy (HCM) is one of the most common human monogenic disorders with the prevalence estimates of 1:500, predicting approximately 600,000 persons with HCM in the US alone. It is also the most common causes for sudden cardiac death among young adults. HCM is generally defined by the development of unexplained left ventricular hypertrophy (LVH) and commonly caused by mutations in cardiac sarcomere genes. In HCM, LVH occurs in a non-dilated ventricle in the absence of other cardiac or systemic disease capable of producing the observed abnormal LV wall thickness. Systemic diseases that can mimic HCM are for example pressure overload due to long-standing hypertension or aortic stenosis, or storage/infiltrative disorders (Fabry disease, Pompe disease) or certain syndromes (Noonan spectrum diseases, Danon disease). The clinical manifestations of HCM range from asymptomatic LVH to progressive heart failure to ventricular arrhythmias and sudden cardiac death (SCD). Atrial fibrillation and atrioventricular conduction abnormalities can also manifest. HCM is the most common cause of sudden cardiac death under age of 30 and also the most common cause for SCD in athletes. SCD can be the first clinical manifestation even in patients with no clear LVH. Symptoms can vary from individual to individual even within the same family. Common symptoms include shortness of breath (particularly during exercise), chest pain, palpitations, orthostasis, presyncope, and syncope. Most often the LVH of HCM becomes apparent during adolescence or young adulthood, although it may also develop later in life, in infancy, or in childhood.


Results in 3-4 weeks. We do not offer a maternal cell contamination (MCC) test at the moment. We offer prenatal testing only for cases where the maternal cell contamination studies (MCC) are done by a local genetic laboratory. Read more: http://blueprintgenetics.com/faqs/#prenatal

Genes in the Hypertrophic Cardiomyopathy (HCM) Panel and their clinical significance
Gene Associated phenotypes Inheritance ClinVar HGMD
ACTC1 Left ventricular noncompaction, Hypertrophic cardiomyopathy (HCM), Cardiomyopathy, restrictive, Atrial septal defect, Dilated cardiomyopathy (DCM) AD 23 38
ACTN2 Hypertrophic cardiomyopathy (HCM), Dilated cardiomyopathy (DCM) AD 10 15
ALPK3 Pediatric cardiomyopathy AR 4
CSRP3 Hypertrophic cardiomyopathy (HCM), Dilated cardiomyopathy (DCM) AD 5 15
GAA Glycogen storage disease AR 79 503
GLA Fabry disease XL 191 885
JPH2 Hypertrophic cardiomyopathy (HCM) AD 4 10
LAMP2 Danon disease XL 46 81
MYBPC3 Left ventricular noncompaction, Hypertrophic cardiomyopathy (HCM), Dilated cardiomyopathy (DCM) AD 390 707
MYH7 Hypertrophic cardiomyopathy (HCM), Myopathy, myosin storage, Myopathy, distal, Dilated cardiomyopathy (DCM) AD 285 748
MYL2 Hypertrophic cardiomyopathy (HCM) AD 20 39
MYL3 Hypertrophic cardiomyopathy (HCM) AD/AR 12 24
PRKAG2 Hypertrophic cardiomyopathy (HCM), Wolff-Parkinson-White syndrome AD 16 24
RAF1 LEOPARD syndrome, Noonan syndrome, Dilated cardiomyopathy (DCM) AD 37 42
SOS1 Noonan syndrome AD 41 66
TNNI3 Hypertrophic cardiomyopathy (HCM), Cardiomyopathy, restrictive, Dilated cardiomyopathy (DCM) AD/AR 55 92
TNNT2 Left ventricular noncompaction, Hypertrophic cardiomyopathy (HCM), Cardiomyopathy, restrictive, Dilated cardiomyopathy (DCM) AD 56 114
TPM1 Hypertrophic cardiomyopathy (HCM), Dilated cardiomyopathy (DCM) AD 36 62
TTR Dystransthyretinemic hyperthyroxinemia, Amyloidosis, hereditary, transthyretin-related AD 51 138

*Some regions of the gene are duplicated in the genome leading to limited sensitivity within the regions. Thus, low-quality variants are filtered out from the duplicated regions and only high-quality variants confirmed by other methods are reported out. Read more.

Gene, refers to HGNC approved gene symbol; Inheritance to inheritance patterns such as autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL); ClinVar, refers to a number of variants in the gene classified as pathogenic or likely pathogenic in ClinVar (http://www.ncbi.nlm.nih.gov/clinvar/); HGMD, refers to a number of variants with possible disease association in the gene listed in Human Gene Mutation Database (HGMD, http://www.hgmd.cf.ac.uk/ac/). The list of associated (gene specific) phenotypes are generated from CDG (http://research.nhgri.nih.gov/CGD/) or Orphanet (http://www.orpha.net/) databases.

Gene Genomic location HG19 HGVS RefSeq RS-number Comment Reference
GAA Chr17:78078341 c.-32-13T>G NM_000152.3 rs386834236
GAA Chr17:78078351 c.-32-3C>A NM_000152.3
GAA Chr17:78082266 c.1076-22T>G NM_000152.3 rs762260678
GLA ChrX:100654735 c.640-801G>A NM_000169.2 rs199473684
MYBPC3 Chr11:47364832 c.1224-19G>A NM_000256.3 rs587776699
MYBPC3 Chr11:47359371 c.2309-26A>G NM_000256.3

The strengths of this test include:

  • Blueprint Genetics is one of the few laboratories worldwide with CAP and ISO-15189 accreditation for NGS panels and CLIA certification
  • Superior sequencing quality
  • Careful selection of genes based on current literature, our experience and the most current mutation databases
  • Transparent and easy access to quality and performance data at the patient level that are accessible via our Nucleus portal
  • Transparent and reproducible analytical validation for each panel (see Test performance section; for complete details, see our Analytic Validation)
  • Sequencing and high resolution del/dup analysis available in one test
  • Inclusion of non-coding disease causing variants where clinically indicated (please see individual Panel descriptions)
  • Interpretation of variants following ACMG variant classification guidelines
  • Comprehensive clinical statement co-written by a PhD geneticist and a clinician specialist


This test does not detect the following:

  • Complex inversions
  • Gene conversions
  • Balanced translocations
  • Mitochondrial DNA variants
  • Variants in regulatory or non-coding regions of the gene unless otherwise indicated (please see Non-coding disease causing variants covered by the panel). This mean for instance intronic variants locating deeper than 15 nucleotides from the exon-intron boundary.


This test may not reliably detect the following:

  • Low level mosaicism
  • Stretches of mononucleotide repeats
  • Indels larger than 50bp
  • Single exon deletions or duplications
  • Variants within pseudogene regions/duplicated segments
  • Disorders caused by long repetitive sequences (e.g. trinucleotide repeat expansions)


The sensitivity of this test may be reduced if DNA is extracted by a laboratory other than Blueprint Genetics.

For additional information, please refer to the Test performance section and see our Analytic Validation.

Blueprint Genetics offers a comprehensive Hypertrophic Cardiomyopathy (HCM) Panel that covers classical genes associated with cardiomagaly, hypertrophic cardiomyopathy (HCM), obstructive HCM and RCM. The genes are carefully selected based on the existing scientific evidence, our experience and most current mutation databases. Candidate genes are excluded from this first-line diagnostic test. The test does not recognise balanced translocations or complex inversions, and it may not detect low-level mosaicism. The test should not be used for analysis of sequence repeats or for diagnosis of disorders caused by mutations in the mitochondrial DNA.

Analytical validation is a continuous process at Blueprint Genetics. Our mission is to improve the quality of the sequencing process and each modification is followed by our standardized validation process. Average sensitivity and specificity in Blueprint NGS Panels is 99.3% and 99.9% for detecting SNPs. Sensitivity to for indels vary depending on the size of the alteration: 1-10bps (96.0%), 11-20 bps (88.4%) and 21-30 bps (66.7%). The longest detected indel was 46 bps by sequence analysis. Detection limit for Del/Dup (CNV) analysis varies through the genome depending on exon size, sequencing coverage and sequence content. The sensitivity is 71.5% for single exon deletions and duplications and 99% for three exons’ deletions and duplications. We have validated the assays for different starting materials including EDTA-blood, isolated DNA (no FFPE) and saliva that all provide high-quality results. The diagnostic yield varies substantially depending on the used assay, referring healthcare professional, hospital and country. Blueprint Genetics’ Plus Analysis (Seq+Del/Dup) maximizes the chance to find molecular genetic diagnosis for your patient although Sequence Analysis or Del/Dup Analysis may be cost-effective first line test if your patient’s phenotype is suggestive for a specific mutation profile.

The sequencing data generated in our laboratory is analyzed with our proprietary data analysis and annotation pipeline, integrating state-of-the art algorithms and industry-standard software solutions. Incorporation of rigorous quality control steps throughout the workflow of the pipeline ensures the consistency, validity and accuracy of results. The highest relevance in the reported variants is achieved through elimination of false positive findings based on variability data for thousands of publicly available human reference sequences and validation against our in-house curated mutation database as well as the most current and relevant human mutation databases. Reference databases currently used are the 1000 Genomes Project (http://www.1000genomes.org), the NHLBI GO Exome Sequencing Project (ESP; http://evs.gs.washington.edu/EVS), the Exome Aggregation Consortium (ExAC; http://exac.broadinstitute.org), ClinVar database of genotype-phenotype associations (http://www.ncbi.nlm.nih.gov/clinvar) and the Human Gene Mutation Database (http://www.hgmd.cf.ac.uk). The consequence of variants in coding and splice regions are estimated using the following in silico variant prediction tools: SIFT (http://sift.jcvi.org), Polyphen (http://genetics.bwh.harvard.edu/pph2/), and Mutation Taster (http://www.mutationtaster.org).

Through our online ordering and statement reporting system, Nucleus, the customer can access specific details of the analysis of the patient. This includes coverage and quality specifications and other relevant information on the analysis. This represents our mission to build fully transparent diagnostics where the customer gains easy access to crucial details of the analysis process.

In addition to our cutting-edge patented sequencing technology and proprietary bioinformatics pipeline, we also provide the customers with the best-informed clinical report on the market. Clinical interpretation requires fundamental clinical and genetic understanding. At Blueprint Genetics our geneticists and clinicians, who together evaluate the results from the sequence analysis pipeline in the context of phenotype information provided in the requisition form, prepare the clinical statement. Our goal is to provide clinically meaningful statements that are understandable for all medical professionals, even without training in genetics.

Variants reported in the statement are always classified using the Blueprint Genetics Variant Classification Scheme modified from the ACMG guidelines (Richards et al. 2015), which has been developed by evaluating existing literature, databases and with thousands of clinical cases analyzed in our laboratory. Variant classification forms the corner stone of clinical interpretation and following patient management decisions. Our statement also includes allele frequencies in reference populations and in silico predictions. We also provide PubMed IDs to the articles or submission numbers to public databases that have been used in the interpretation of the detected variants. In our conclusion, we summarize all the existing information and provide our rationale for the classification of the variant.

A final component of the analysis is the Sanger confirmation of the variants classified as likely pathogenic or pathogenic. This does not only bring confidence to the results obtained by our NGS solution but establishes the mutation specific test for family members. Sanger sequencing is also used occasionally with other variants reported in the statement. In the case of variant of uncertain significance (VUS) we do not recommend risk stratification based on the genetic finding. Furthermore, in the case VUS we do not recommend use of genetic information in patient management or genetic counseling. For some cases Blueprint Genetics offers a special free of charge service to investigate the role of identified VUS.

We constantly follow genetic literature adapting new relevant information and findings to our diagnostics. Relevant novel discoveries can be rapidly translated and adopted into our diagnostics without delay. These processes ensure that our diagnostic panels and clinical statements remain the most up-to-date on the market.

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ICD & CPT codes

CPT codes

SEQ 81479
DEL/DUP 81479

ICD codes

Commonly used ICD-10 codes when ordering the Hypertrophic Cardiomyopathy (HCM) Panel

ICD-10 Disease
I42.5 RCM
I42.1 Obstructive HCM
I42.2 Hypertrophic cardiomyopathy (HCM)

Accepted sample types

  • EDTA blood, min. 1 ml
  • Purified DNA, min. 5μg
  • Saliva (Oragene DNA OG-500 kit)

Label the sample tube with your patient’s name, date of birth and the date of sample collection.

Note that we do not accept DNA samples isolated from formalin-fixed paraffin-embedded (FFPE) tissue.

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