Test Id : HCMGP

Targeted testing for familial variants (also called site-specific or known mutations testing) is available for the genes on this panel. See FMTT / Familial Mutation, Targeted Testing, Varies.

1. Hereditary Cardiomyopathies and Arrhythmias: Patient Information (T725) is strongly recommended, but not required, to be filled out and sent with the specimen. This information aids in providing a more thorough interpretation of test results. Ordering providers are strongly encouraged to complete the form and send it with the specimen.

2. Include physician name and phone number with specimen.

3. Prior Authorization is available for this test. Submit the required form with the specimen.

Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.

Container/Tube: Lavender top (EDTA)

Specimen Volume: 3 mL

Collection Instructions: Send specimen in original tube. Do not aliquot.

• Informed Consent for Genetic Testing
• Hypertrophic Cardiomyopathy Multi-Gene Panel Prior Authorization Ordering Instructions
• Hereditary Cardiomyopathies and Arrhythmias: Patient Information
• Informed Consent for Genetic Testing (Spanish)

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. Hereditary Cardiomyopathies and Arrhythmias: Patient Information (T725) is recommended.

3. Hypertrophic Cardiomyopathy Multi-Gene Panel Prior Authorization Ordering Instructions.

4. If not ordering electronically, complete, print, and send a Cardiovascular Test Request Form (T724) with the specimen.

1 mL

Providing a comprehensive genetic evaluation for patients with a personal or family history suggestive of hereditary hypertrophic cardiomyopathy (HCM)

Establishing a diagnosis of a hereditary HCM, and in some cases, allowing for appropriate management and surveillance for disease features based on the gene involved

Identifying a pathogenic variant within a gene known to be associated with disease that allows for predictive testing of at-risk family members

This test uses next-generation sequencing to test for variants in the ACTC1, ACTN2, ANKRD1, CAV3, CSRP3, DES, GLA, LAMP2, MYBPC3, MYH7, MYL2, MYL3, MYLK2, MYOZ2, NEXN, PLN, PRKAG2, RAF1, TCAP, TNNC1, TNNI3, TNNT2, TPM1, TTN (excluding the following genomic regions: Chr2(GRCh37):g. 179523879-179524002 and Chr2(GRCh37):g. 179523712-179523835), TTR, and VCL genes.

This test uses Sanger sequencing to test for variants in exon 27 of the MYH7 gene.

Identification of a pathogenic variant may assist with prognosis, clinical management, familial screening, and genetic counseling.

Prior Authorization is available for this assay.

The cardiomyopathies are a group of disorders characterized by disease of the heart muscle. Cardiomyopathy can be caused by inherited, genetic factors, or by nongenetic (acquired) causes such as infection or trauma. When the presence or severity of the cardiomyopathy observed in a patient cannot be explained by acquired causes, genetic testing for the inherited forms of cardiomyopathy may be considered. Overall, the cardiomyopathies are some of the most common genetic disorders. The inherited forms of cardiomyopathy include hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), and left ventricular noncompaction (LVNC).

The hereditary form of HCM is characterized by left ventricular hypertrophy in the absence of other cardiac or systemic causes that may cause hypertrophy of the heart muscle, such as longstanding, uncontrolled hypertension or aortic stenosis. The pathological hallmark of HCM is "myocyte disarray" where there is a loss of parallel alignment of myocytes in the heart wall. HCM is most often caused by genes encoding the cardiac sarcomere, the functional contractile unit of the heart muscle. The clinical presentation of HCM can be variable, even within the same family. HCM can be asymptomatic in some individuals, but can cause life-threatening arrhythmias, which increase the risk of sudden cardiac death. The incidence of HCM in the general population is approximately 1 in 500. Inheritance is autosomal dominant, but compound heterozygosity (biallelic variants in the same gene) and digenic inheritance (variants in 2 different HCM-associated genes) do occur.

The MYBPC3, MYL2, MYL3, MYH7, ACTC, TPM1, TNNI3, TNNT2, and CAV3 genes are involved in formation and regulation of the cardiac sarcomere, and account for the majority of variants in HCM. Left ventricular hypertrophy can also be caused by metabolic or storage disorders such as Fabry disease (GLA gene), Danon disease (LAMP2 gene), and Wolf-Parkinson-White syndrome associated with variants in the PRKAG2 gene. The TTR gene causes familial transthyretin amyloidosis, which is characterized by buildup of amyloid protein that affects the peripheral and autonomic nervous system. Other nonneuropathic changes may also be involved, including cardiomyopathy. See table for details regarding the genes tested by this panel and associated diseases.

Genes included in this panel

Abbreviations not previously defined: Congenital heart defects (CHD), long QT syndrome (LQTS), limb-girdle muscular dystrophy (LGMD), autosomal dominant (AD), autosomal recessive (AR)

An interpretive report will be provided.

Evaluation and categorization of variants is performed using the most recent published American College of Medical Genetics and Genomics (ACMG) recommendations as a guideline.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Multiple in silico evaluation tools may be used to assist in the interpretation of these results. The accuracy of predictions made by in silico evaluation tools is highly dependent upon the data available for a given gene, and predictions made by these tools may change over time. Results from in silico evaluation tools should be interpreted with caution and professional clinical judgment.

Clinical Correlations:

Some individuals who have involvement of one or more of the genes on the panel may have a variant that is not identified by the methods performed (eg, promoter variants, deep intronic variants). The absence of a variant, therefore, does not eliminate the possibility of a hereditary hypertrophic cardiomyopathy or a related disorder.

Test results should be interpreted in context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.

If testing was performed because of a family history of hereditary hypertrophic cardiomyopathy or a related disorder, it is often useful to first test an affected family member. Identification of a pathogenic variant in an affected individual allows for more informative testing of at-risk individuals.

Technical Limitations:

Next-generation sequencing may not detect all types of genetic variants. Additionally, rare alterations (ie, polymorphisms) may be present that could lead to false-negative or false-positive results. If results do not match clinical findings, consider alternative methods for analyzing these genes, such as Sanger sequencing or large deletion/duplication analysis.

If the patient has had an allogeneic blood or marrow transplant or a recent (ie, <6 weeks from time of sample collection) heterologous blood transfusion, results may be inaccurate due to the presence of donor DNA.

Reclassification of Variants Policy:

At this time, it is not standard practice for the laboratory to systematically review likely pathogenic variants or variants of uncertain significance that are detected and reported. The laboratory encourages health care providers to contact the laboratory at any time to learn how the status of a particular variant may have changed over time. Consultation with a genetics professional should be considered for interpretation of this result.

A list of benign and likely benign variants detected for this patient is available from the laboratory upon request.

Contact the laboratory if additional information is required regarding the transcript or human genome assembly used for the analysis of this patient's results.

1. Richards S, Aziz N, Bale 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 May;17(5):405-424

2. Cirino AL, Ho C: Hypertrophic cardiomyopathy overview. In: Adam MP, Ardinger HH, Pagon RA, et al. eds. GeneReviews [Internet]. University of Washington, Seattle; 2008. Updated July 8, 2021. Accessed September 13, 2021. Available at www.ncbi.nlm.nih.gov/books/NBK1768/

3. Callis TE, Jensen BC, Weck KE, Willis MS: Evolving molecular diagnostics for familial cardiomyopathies: at the heart of it all. Expert Rev Mol Diagn. 2010 April;10:3:329-351

4. Marian AJ, Roberts R: Molecular genetics of hypertrophic cardiomyopathy. Ann Rev Med. 1995;46:213-222

5. van Rijsingen IA, Hermans-van Ast JF, Arens YH, et al: Hypertrophic cardiomyopathy family with double-heterozygous mutations; does disease severity suggest double heterozygosity? Neth Heart J. 2009;17:458-463

6. Woo A, Rakowski H, Liew JC, et al: Mutations of the beta myosin heavy chain gene in hypertrophic cardiomyopathy: critical functional sites determine prognosis. Heart. 2003;89:1179-1185

7. Maron BJ, McKenna WJ, Danielson GK, et al: American College of Cardiology/European Society of Cardiology clinical expert consensus document on hypertrophic cardiomyopathy. A report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for Practice Guidelines. J Am Coll Cardiol. 2003;42(9):1687-1713

8. Ackerman MJ, Priori SG, Willems S, et al: HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies. Heart Rhythm. 2011;8:1308-1339

• Informed Consent for Genetic Testing
• Hypertrophic Cardiomyopathy Multi-Gene Panel Prior Authorization Ordering Instructions
• Hereditary Cardiomyopathies and Arrhythmias: Patient Information
• Informed Consent for Genetic Testing (Spanish)

Next-generation sequencing (NGS) is performed using an Illumina instrument with paired-end reads. The DNA is prepared for NGS using a custom Agilent SureSelect Target Enrichment System. Data is analyzed with a bioinformatics software pipeline. Supplemental and confirmatory Sanger sequencing are performed when necessary.(Unpublished Mayo method)

Genes analyzed: ACTC1, ACTN2, ANKRD1, CAV3, CSRP3, DES, GLA, LAMP2, MYBPC3, MYH7, MYL2, MYL3, MYLK2, MYOZ2, NEXN, PLN, PRKAG2, RAF1, TCAP, TNNC1, TNNI3, TNNT2, TPM1, TTN (excluding the following genomic regions: Chr2(GRCh37):g. 179523879-179524002 and Chr2(GRCh37):g. 179523712-179523835), TTR, and VCL.

Monday

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This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

81439

Insurance preauthorization is available for this testing; forms are available.

Sample Reports

Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports

International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports