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Test Catalog

Test ID: DCMGP    
Dilated Cardiomyopathy Multi-Gene Panel, Next-Generation Sequencing, 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 dilated cardiomyopathy (DCM)

 

Establishing a diagnosis of a hereditary DCM, 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 features 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 ABCC9, ACTC1, ACTN2, ANKRD1, CRYAB, CSRP3, DES, LAMA4, LAMP2, LDB3, LMNA, MYBPC3, MYH6, MYH7, MYPN, NEXN, PLN, RAF1, RBM20, SCN5A, SGCD, TAZ, 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 certain exons of the following genes:

MYH6 exon 26

MYH7 exon 27

 

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

 

Prior Authorization is available for this assay; see Special Instructions.

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).

 

DCM is established by the presence of left ventricular enlargement and systolic dysfunction. DCM may present with heart failure with symptoms of congestion, arrhythmias, and conduction system disease, or thromboembolic disease (stroke). The most recent estimates of the incidence of DCM suggest that the condition affects approximately 1 in every 250 people. These estimates are higher than originally reported due to subclinical phenotypes and underdiagnosis. After exclusion of nongenetic causes such as ischemic injury, DCM is traditionally referred to as "idiopathic" dilated cardiomyopathy. Approximately 20% to 50% of individuals with idiopathic DCM may have an identifiable genetic cause for their disease. Families with 2 or more affected individuals are diagnosed with familial dilated cardiomyopathy. 

 

The majority of familial dilated cardiomyopathy is inherited in an autosomal dominant manner; however, autosomal recessive and X-linked forms have also been reported. At least 28 genes have been reported in association with DCM, including genes encoding the cardiac sarcomere and other proteins involved in proteins responsible for cardiac muscle contraction. Some genes associated with DCM also cause other forms of hereditary cardiomyopathy, cardiac channelopathies, skeletal myopathies, or metabolic defects. See table for details regarding the genes tested by this panel and associated diseases.

 

Genes included in the Dilated Cardiomyopathy Multi-Gene Panel

Gene

Protein

Inheritance

Disease Association

ABCC9

ATP-Binding cassette, subfamily C, member 9

AD

DCM, Cantu syndrome

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

CRYAB

Crystallin, alpha-B

AD, AR

DCM, myofibrillar myopathy

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

LAMA4

Laminin, alpha-4

AD

DCM

LAMP2

Lysosome-associated membrane protein 2

X-linked

Danon disease

LDB3

LIM domain-binding 3

AD

DCM, LVNC, myofibrillar myopathy

LMNA

Lamin A/C

AD, AR

DCM, EMD, LGMD, congenital muscular dystrophy (see OMIM for full listing)

MYBPC3

Myosin-binding protein-C, cardiac

AD

HCM, DCM

MYH6

Myosin, heavy chain 6, cardiac muscle, alpha

 

HCM, DCM

MYH7

Myosin, heavy chain 7, cardiac muscle, beta

AD

HCM, DCM, LVNC, myopathy

MYPN

Myopalladin

AD

HCM, DCM

NEXN

Nexilin

AD

HCM, DCM

PLN

Phospholamban

AD

HCM, DCM

RAF1

V-raf-1 murine leukemia viral oncogene homolog 1

AD

Noonan/multiple lentigines syndrome, DCM

RBM20

RNA-binding motif protein 20

AD

DCM

SCN5A

Sodium channel, voltage gated, type V, alpha subunit

AD

Brugada syndrome, DCM, Heart block, LQTS, SSS, SIDS

SGCD

Sarcoglycan, delta

AD, AR

DCM, LGMD

TAZ

Tafazzin

X-linked

Barth syndrome, LVNC, DCM

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, ARVC myopathy

TTR

Transthyretin

AD

Transthyretin-related amyloidosis

VCL

Vinculin

AD

HCM, DCM

Abbreviations: Hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), left ventricular noncompaction cardiomyopathy (LVNC), restrictive cardiomyopathy (RCM), limb-girdle muscular dystrophy (LGMD), Emory muscular dystrophy (EMD), congenital heart defects (CHD), sudden infant death syndrome (SIDS), long QT syndrome (LQTS), sick sinus syndrome (SSS), 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. 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 1 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 dilated cardiomyopathy (DMC) 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 DMC 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 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, less than 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. Hershberger RE, Kushner JD, Parks SB: Dilated Cardiomyopathy Overview. In GeneReviews. 2007. Available at www.genetests.org

2. Hunt SA, Abraham WT, Chin MH, et al: ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult. Circulation 2005;112:e154-e235

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. Herman DS, Lam L, Taylor MR, et al: Truncations of titin causing dilated cardiomyopathy. N Engl J Med 2012;366(7):619-628

5. Dhandapany PS, Razzaque MA, Muthusami U, et al: RAF1 mutations in childhood-onset dilated cardiomyopathy. Nat Genet 2014;46(6):635-639

6. Hershberger RE, Morales A: Dilated Cardiomyopathy Overview. In GeneReviews. Edited by RA Pagon, MP Adam, HH Ardinger, et al. University of Washington, Seattle. 1993-2018. Updated 2015 Sep 24. Accessed June 2018. Available at www.ncbi.nlm.nih.gov/books/NBK1309/

7. Ackerman M, 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