Test Catalog

Test Id : HCMGP

Hypertrophic Cardiomyopathy Multi-Gene Panel, Blood

Useful For
Suggests clinical disorders or settings where the test may be helpful

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

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

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.

Highlights

This test includes next-generation sequencing and supplemental Sanger sequencing to evaluate the genes tested on this panel.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

Sequence Capture and Targeted Next-Generation Sequencing followed by Polymerase Chain Reaction (PCR) and supplemental Sanger Sequencing

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Hypertrophic Cardiomyopathy Panel,B

Aliases
Lists additional common names for a test, as an aid in searching

Cardiomyopathy

Hypertrophic cardiomyopathy (HCM)

HCM

ACTC1

ACTN2

ANKRD1

CAV3

CSRP3

DES

GLA

LAMP2

MYBPC3

MYH7

MYL2

MYL3

MYLK2

MYOZ2

NEXN

PLN

PRKAG2

RAF1

TCAP

TNNC1

TNNI3

TNNT2

TPM1

TTN

TTR

VCL

Next Gen Sequencing Test

Specimen Type
Describes the specimen type validated for testing

Whole Blood EDTA

Ordering Guidance

Necessary Information

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.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

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.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Forms

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.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

1 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Whole Blood EDTA Ambient (preferred)
Refrigerated

Useful For
Suggests clinical disorders or settings where the test may be helpful

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

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

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.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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

Gene

Protein

Inheritance

Disease association

ACTC1

Actin, alpha, cardiac muscle

AD

CHD, DCM, HCM, LVNC

ACTN2

Actinin, alpha-2

AD

DCM, HCM

ANKRD1

Ankyrin repeat domain-containing protein 1

AD

HCM, DCM

CAV3

Caveolin 3

AD, AR

HCM, LQTS, LGMD, Tateyama-type distal myopathy, rippling muscle disease

CSRP3

Cysteine-and glycine-rich protein 3

AD

HCM, DCM

DES

Desmin

AD, AR

DCM, ARVC, myofibrillar myopathy, RCM with AV block, neurogenic scapuloperoneal syndrome Kaeser type, LGMD

GLA

Galactosidase, alpha

X-linked

Fabry disease

LAMP2

Lysosome-associated membrane protein 2

X-linked

Danon disease

MYBPC3

Myosin-binding protein-C, cardiac

AD

HCM, DCM

MYH7

Myosin, heavy chain 7, cardiac muscle, beta

AD

HCM, DCM, LVNC, myopathy

MYL2

Myosin, light chain 2, regulatory, cardiac, slow

AD

HCM

MYL3

Myosin, light chain 3, alkali, ventricular, skeletal, slow

AD, AR

HCM

MYLK2

Myosin light chain kinase 2

AD

HCM

MYOZ2

Myozenin 2

AD

HCM

NEXN

Nexilin

AD

HCM, DCM

PLN

Phospholamban

AD

HCM, DCM

PRKAG2

Protein kinase, amp-activated, noncatalytic, gamma2

AD

HCM, Wolff-Parkinson-White syndrome

RAF1

V-RAF-1 murine leukemia viral oncogene homolog 1

AD

Noonan/multiple lentigines syndrome

TCAP

Titin-cap (telethonin)

AD, AR

HCM, DCM, LGMD

TNNC1

Troponin C, slow

AD

HCM, DCM

TNNI3

Troponin I, cardiac

AD, AR

DCM, HCM, RCM

TNNT2

Troponin T2, cardiac

AD

HCM, DCM, RCM, LVNC

TPM1

Tropomyosin 1

AD

HCM, DCM, LVNC

TTN

Titin

AD, AR

HCM, DCM, myopathy

TTR

Transthyretin

AD

Transthyretin-related amyloidosis

VCL

Vinculin

AD

HCM, DCM

 

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

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation
Provides information to assist in interpretation of the test results

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.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

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.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

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

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

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.

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

4 to 6 weeks after prior authorization approved

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

Extracted DNA: 2 months

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

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.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

81439

Prior Authorization
Prior Authorization may be required by your insurance carrier.

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

 

Patient financial assistance may be available to those who qualify. Patients who receive a bill from Mayo Clinic Laboratories will receive information on eligibility and how to apply.

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
HCMGP Hypertrophic Cardiomyopathy Panel,B In Process
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
36806 Gene(s) Evaluated 48018-6
36807 Result Summary 50397-9
36808 Result Details 82939-0
36809 Interpretation 69047-9
36944 Additional Information 48767-8
36945 Method 85069-3
36946 Disclaimer 62364-5
36810 Reviewed by 18771-6

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

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

Test Update Resources

Change Type Effective Date
Obsolete Test 2022-12-15