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HelpTest 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
Special Instructions
Reporting Name
Arrhythmogenic Cardiomyopathy, BSpecimen Type
Whole Blood EDTAAdvisory 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 approvedTest 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).
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