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Test ID: ARVGP Arrhythmogenic Cardiomyopathy Multi-Gene Panel, Blood

Useful For

Providing a comprehensive genetic evaluation for patients with a personal or family history suggestive of hereditary arrhythmogenic right ventricular cardiomyopathy (ARVC or AC)

 

Establishing a diagnosis of ARVC or AC, 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

Reporting Name

Arrhythmogenic Cardiomyopathy, B

Specimen Type

Whole Blood EDTA


Advisory Information


Targeted testing for familial variants (also called site-specific or known mutation testing) is available for this gene.

-KVAR1 / Known Variant Analysis-1 Variant

-KVAR2 / Known Variant Analysis-2 Variants

-KVAR3 / Known Variant Analysis-3+ Variants



Necessary Information


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

0.6 mL

Specimen Stability Information

Specimen Type Temperature Time
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 or AC), and left ventricular noncompaction (LVNC).

 

Arrhythmogenic right ventricular dysplasia (ARVD or AC), is characterized by breakdown of the myocardium and replacement of the muscle tissue with fibrofatty tissue, resulting in an increased risk of arrhythmia and sudden death. The incidence of ARVC is approximately 1 in 1,000 to 1 in 2,500. Age of onset and severity are variable, but symptoms typically develop in adulthood. ARVC is present in 4% to 22% of athletes with sudden cardiac death, and there is some debate whether high-intensity endurance exercise may cause development of ARVC.

 

ARVC is typically considered a disease of the desmosome, the structure that attaches heart muscle cells to one another. The desmosome provides strength to the muscle tissue and plays a role in signaling between neighboring cells. Variants in the genes associated with ARVC disrupt this function, causing detachment and death of myocardial cells when the heart muscle is under stress. Damaged myocardium is replaced with fat and scar tissue, eventually leading to structural and electrical abnormalities that can lead to arrhythmia.

 

Inheritance of ARVC typically follows an autosomal dominant pattern of inheritance, and variants in DSC2, DSP, and PKP2 account for approximately half of the variants identified in ARVC. However, simultaneous testing of all known ARVC genes is recommended due to the potential for compound heterozygosity (biallelic variants on the same gene) or digenic heterozygosity (variants in 2 different genes). See table for details regarding the genes tested by this panel and associated diseases.

 

Genes included in the Arrhythmogenic Cardiomyopathy Multi-Gene Panel

Gene

Protein

Inheritance

Disease Association

DES

Desmin

AD, AR

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

DSC2

Desmocollin

AD, AR

ARVC, ARVC + skin and hair findings

DSG2

Desmoglein

AD

ARVC

DSP

Desmoplakin

AD, AR

ARVC, DCM, Carvajal syndrome

JUP

Junction plakoglobin

AD, AR

ARVC, Naxos disease

LMNA

Lamin A/C

AD, AR

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

PKP2

Plakophilin 2

AD

ARVC

RYR2

Ryanodine receptor 2

AD

ARVC, CPVT, LQTS

TMEM43

Transmembrane protein 43

AD

ARVC, EMD

TTN

Titin

AD, AR

HCM, DCM, ARVC, myopathy

Abbreviations: Hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), restrictive cardiomyopathy (RCM), limb-girdle muscular dystrophy (LGMD), Emory muscular dystrophy (EMD), catecholaminergic polymorphic ventricular tachycardia (CPVT), long QT syndrome (LQTS), autosomal dominant (AD), autosomal recessive (AR)

Reference Values

An interpretive report will be provided. 

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.

Clinical Reference

1. McNally E, MacLeod H, Dellefave-Castillo L: Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy. In GeneReviews. Edited by RA Pagon, MP Adam, HH Ardinger, et al. University of Washington, Seattle. 1993-2018. Updated 2017 May 25. Accessed June 2018. Available at www.ncbi.nlm.nih.gov/books/NBK1131/

2. 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

3. Taylor M, Graw S, Sinagra G, et al: Genetic variation in titin in arrhythmogenic right ventricular cardiomyopathy-overlap syndromes. Circulation 2011;124.9:876-885

Day(s) and Time(s) Performed

Wednesday; Varies

Analytic Time

4 weeks after prior authorization approved

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.

CPT Code Information

81439

LOINC Code Information

Test ID Test Order Name Order LOINC Value
ARVGP Arrhythmogenic Cardiomyopathy, B In Process

 

Result ID Test Result Name Result LOINC Value
36816 Gene(s) Evaluated 36908-2
36817 Result Summary 50397-9
36818 Result Details 82939-0
36819 Interpretation In Process
36950 Additional Information 48767-8
36951 Method 49549-9
36952 Disclaimer 62364-5
36820 Reviewed by 18771-6

Method Name

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

Forms

1. Hereditary Cardiomyopathies and Arrhythmias: Patient Information (T725) is required. See Special Instructions.

2. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (T576) is available in Special Instructions.

3. Arrhythmogenic Cardiomyopathy Multi-Gene Panel Prior Authorization Ordering Instructions in Special Instructions

4. If not ordering electronically, complete, print, and send a Cardiovascular Test Request Form (T724) with the specimen (http://www.mayomedicallaboratories.com/it-mmfiles/cardiovascular-request-form.pdf).

Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

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