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Test ID: DCMGP Dilated Cardiomyopathy Multi-Gene Panel, Next-Generation Sequencing, Blood

Useful For

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

Reporting Name

Dilated Cardiomyopathy Panel, B

Specimen Type

Whole Blood EDTA


Advisory Information


Targeted testing for familial variants (also called site-specific or known mutation testing) is available for the genes on this panel. See:

-KVAR1 / Known Variant Analysis-1 Variant, Varies

-KVAR2 / Known Variant Analysis-2 Variants, Varies

-KVAR3 / Known Variant Analysis-3+ Variants, Varies

 

Call 800-533-1710 to confirm the appropriate test for targeted testing.



Necessary Information


1. Hereditary Cardiomyopathies and Arrhythmias: Patient Information (T725) is required, see Special Instructions. Testing may proceed without the patient information however it aids in providing a more thorough interpretation. Ordering providers are strongly encouraged to complete the form and send it with the specimen.

2. Include physician name and phone number with specimen.



Specimen Required


Container/Tube: Lavender top (EDTA)

Specimen Volume: 3 mL

Collection Instructions: Send specimen in original tube.

Additional Information: Prior Authorization is available for this test. Submit the required form with the specimen.


Specimen Minimum Volume

1 mL

Specimen Stability Information

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

Clinical Information

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

An interpretive report will be provided. 

Clinical Reference

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

Day(s) and Time(s) Performed

Wednesday; Varies

Analytic Time

4 weeks after prior authorization approved

CPT Code Information

81439

LOINC Code Information

Test ID Test Order Name Order LOINC Value
DCMGP Dilated Cardiomyopathy Panel, B In Process

 

Result ID Test Result Name Result LOINC Value
36811 Gene(s) Evaluated 36908-2
36812 Result Summary 50397-9
36813 Result Details 82939-0
36814 Interpretation 69047-9
36947 Additional Information 48767-8
36948 Method 49549-9
36949 Disclaimer 62364-5
36815 Reviewed by 18771-6

Test Classification

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 U.S. Food and Drug Administration.

Method Name

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

Interpretation

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.

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 in Special Instructions:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing (Spanish) (T826)

2. Dilated Cardiomyopathy Multi-Gene Panel Prior Authorization Ordering Instructions in Special Instruction

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

Mayo Clinic Laboratories | Cardiology Catalog Additional Information:

mml-cardio-ngs