Invitae Hypertrophic Cardiomyopathy Panel


Test description

This test is for individuals with a clinical diagnosis of hypertrophic cardiomyopathy (HCM). The primary Invitae Hypertrophic Cardiomyopathy Panel includes 25 genes that are definitively associated with HCM or with other inherited cardiomyopathy disorders that may present with clinical features similar to HCM.

Individuals with clinical symptoms of HCM may benefit from diagnostic genetic testing to better understand risks, confirm a diagnosis, or inform management. Asymptomatic individuals who have a known familial pathogenic variant may also benefit, as testing may clarify their own personal risk of developing HCM and allow for consideration of medical management. This panel evaluates for syndromic conditions that can mimic HCM. Individuals with apparently isolated HCM may be identified to have a multi-system disorder with left ventricular hypertrophy as the presenting feature.

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Primary panel (25 genes)


GAA: Analysis includes the promoter variant NM_000152.3:c.-32-13T>G as well as the common exon 18 deletion.
GLA: Analysis includes the intronic variant NM_000169.2:c.IVS4+919G>A.
MYBPC3: Analysis includes the intronic variant NM_000256.3:c.3628-41_3628-17del25.

Add-on preliminary-evidence genes (12 genes)

Preliminary-evidence genes currently have early evidence of a clinical association with the specific disease covered by this test. Some clinicians may wish to include genes which do not currently have a definitive clinical association, but which may prove to be clinically significant in the future. These genes can be added at no additional charge. Visit our Preliminary-evidence genes page to learn more.


ANKRD1: Deletion/duplication analysis is not offered for exons 3 or 4.

Add-on RASopathy genes (16 genes)

Structural heart defects or hypertrophic cardiomyopathy are also a common feature of RASopathy conditions. Clinicians can also choose to include genes associated with RASopathy conditions when placing their order at no additional charge.


Add-on autosomal recessive syndromic pediatric cardiomyopathy genes (3 genes)

Genes associated with early-onset cardiomyopathy as part of an autosomal recessive disorder may be included at no additional charge. Clinicians may wish to include these genes for patients who present in infancy or early childhood with clinical features of a multi-system disorder.


Alternative tests to consider

Hypertrophic cardiomyopathy can also be ordered as part of broader panels to test for cardiomyopathy disorders. Depending on the individual’s family history, one of these broader panels may be appropriate. Any of these broader panels can be ordered at no additional charge.

  • Hypertrophic cardiomyopathy (HCM)
  • Danon disease
  • Fabry disease,
  • transthyretin amyloidosis
  • Wolff-Parkinson-White syndrome

Some of these genes on this panel are also associated with other disorders.

Hypertrophic cardiomyopathy (HCM) is a cardiac disorder defined by abnormal thickening of the heart muscle, or myocardium. This abnormal thickening, or hypertrophy, affects the left ventricle of the heart and can typically be detected by echocardiogram. HCM can impair both how the heart contracts and the heart’s electrical system, leading to palpitations, dizziness (pre-syncope), fainting (syncope), chest pain, shortness of breath, and, in some cases, sudden cardiac arrest.

The most common forms of HCM are caused by genetic changes that alter the structure or function of the sarcomere complex, whose primary role is muscle contraction. Altering the sarcomere complex leads to enlargement and misalignment (myocyte disarray) of the heart muscle cells.

HCM is usually diagnosed when there is hypertrophy of the heart muscle identified on echocardiography with the absence of other medical conditions that could cause hypertrophy. Other medical conditions that can cause hypertrophy of the heart muscle include, but are not limited to, long-standing high blood pressure, aortic stenosis, and such multisystem disorders as Fabry disease, familial transthyretin amyloidosis, Danon’s disease, and myofibrillar myopathy. Noonan syndrome is a relatively common multisystem disorder that may present with HCM.

This test covers all of the common genetic causes of HCM. Most cases of HCM are caused by one of several genes that encode sarcomere or sarcomere-associated proteins. Pathogenic variants in one of these genes are identified in up to 40% of HCM cases with no family history and in up to 60% of HCM cases with a family history of HCM.

Two or more pathogenic mutations in sarcomere genes are observed in up to 5% of individuals with HCM and may be associated with an earlier age of onset.

HCM is an autosomal dominant disorder. Fabry disease and Danon disease are X-linked disorders. Pompe disease, glycogen storage disease type III, ELAC2-related and MTO1-related combined oxidative phosphorylation deficiency are autosomal recessive conditions.

In the United States, HCM is one of the most common monogenic (single gene) inherited cardiovascular conditions; it is also the most common cause of sudden cardiac death in athletes. However, HCM exhibits reduced penetrance, as not everyone who inherits a predisposition to develop HCM will go on to manifest symptoms.

Hypertrophic cardiomyopathy affects an estimated 1 in 500 individuals, though recently, the prevalence has been suggested to be as high as 1 in 200 individuals. HCM can present from infancy through adulthood.

This test may be considered for individuals with:

  • unexplained cardiac arrest
  • a clinical diagnosis of HCM based on examination of the patient’s clinical history, family history, and electrocardiographic/echocardiographic phenotype

  1. Ackerman MJ, 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). 2011 Heart Rhythm Aug; 8(8):1308-1339. PMID: 21787999
  2. Gersh, B., et al. 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. 2011: Circulation, 124(24):2761-96. PMID: 22068435
  3. Hershberger RE, et al. Genetic evaluation of cardiomyopathy--a Heart Failure Society of America practice guideline. 2009 J Card Fail. Mar; 15(2):83-97. PMID: 19254666
  4. Ho, C. Genetics and clinical destiny: improving care in hypertrophic cardiomyopathy. Circulation. 2010 Dec 7;122(23):2430-40; discussion 2440. PMID: 21135371
  5. Ingles, J., et al. Compound and double mutations in patients with hypertrophic cardiomyopathy: implications for genetic testing and counselling. J Med Genet. 2005 Oct;42(10):e59. PMID: 16199542
  6. Maron et al. Hypertrophic cardiomyopathy: present and future, with translation into contemporary cardiovascular medicine. J Am Coll Cardiol. 2014 Jul 8;64(1):83-99. PMID: 24998133
  7. NCBI GeneReviews. Hypertrophic Cardiomyopathy Overview. PMID: 20301725
  8. Semsarian C, et al. New perspectives on the prevalence of hypertrophic cardiomyopathy. 2015 J Am Coll Cardiol. Mar 31;65(12):1249-1254. PMID: 25814232

For links to published management guidelines for cardiology conditions, please refer to our Management guidelines page.

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
A2ML1 NM_144670.4
ACADVL NM_000018.3
ACTC1 NM_005159.4
ACTN2 NM_001103.3
AGL NM_000642.2
ANKRD1* NM_014391.2
BAG3 NM_004281.3
BRAF NM_004333.4
CACNA1C NM_000719.6
CALR3 NM_145046.4
CAV3 NM_033337.2
CBL NM_005188.3
CSRP3 NM_003476.4
DES NM_001927.3
ELAC2 NM_018127.6
FHL1 NM_001449.4, NM_001159702.2
GAA* NM_000152.3
GATA4 NM_002052.3
GLA* NM_000169.2
HRAS NM_005343.2
JPH2 NM_020433.4
KRAS NM_004985.4
LAMP2 NM_002294.2, NM_013995.2
LDB3 NM_001080116.1, NM_001171610.1
MAP2K1 NM_002755.3
MAP2K2 NM_030662.3
MTO1 NM_012123.3
MYBPC3* NM_000256.3
MYH6 NM_002471.3
MYH7 NM_000257.3
MYL2 NM_000432.3
MYL3 NM_000258.2
MYLK2 NM_033118.3
MYOM1 NM_003803.3
MYOZ2 NM_016599.4
MYPN NM_032578.3
NEXN NM_144573.3
NF1 NM_000267.3
NRAS NM_002524.4
PDLIM3 NM_014476.5
PLN NM_002667.3
PRKAG2 NM_016203.3
PTPN11 NM_002834.3
RAF1 NM_002880.3
RASA1 NM_002890.2
RIT1 NM_006912.5
SHOC2 NM_007373.3
SOS1 NM_005633.3
SPRED1 NM_152594.2
TCAP NM_003673.3
TNNC1 NM_003280.2
TNNI3 NM_000363.4
TNNT2 NM_001001430.2, NM_000364.3
TPM1 NM_001018005.1
TTR NM_000371.3
VCL NM_014000.2

ANKRD1: Deletion/duplication analysis is not offered for exons 3 or 4.
GAA: Analysis includes the promoter variant NM_000152.3:c.-32-13T>G as well as the common exon 18 deletion.
GLA: Analysis includes the intronic variant NM_000169.2:c.IVS4+919G>A.
MYBPC3: Analysis includes the intronic variant NM_000256.3:c.3628-41_3628-17del25.