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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

Method Name

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

Reporting Name

Arrhythmogenic Cardiomyopathy, B

Specimen Type

Whole Blood EDTA

Container/Tube: Lavender top (EDTA)

Specimen Volume: 3 mL

Collection Instructions: Send specimen in original tube.

Additional Information:

1. Include physician name and phone number with the specimen.

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

Forms:

1. Hereditary Cardiomyopathies and Arrhythmias: Patient Information Sheet (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).

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. 

Cautions

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 arrhythmogenic right ventricular 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 arrhythmogenic right ventricular 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 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.

 

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

Day(s) Performed

Wednesday; Varies

Report Available

4 weeks after prior authorization approved

Performing Laboratory

Mayo Medical Laboratories in Rochester

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

81405 DES

81406 x 7 DSC2, DSG2, DSP, JUP, LMNA, PKP2, TMEM43

81408 RYR2

81479 TTN

NY State Approved

Conditional

Prior Authorization

Insurance preauthorization is available for this testing; forms are available in Special Instructions.

 

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