Test Catalog

Test Id : ARVGP

Arrhythmogenic Cardiomyopathy Multi-Gene Panel, 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 arrhythmogenic right ventricular cardiomyopathy (ARVC or AC)

 

Establishing a diagnosis of ARVC, 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

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 DES, DSC2, DSG2, DSP, JUP, LMNA, PKP2, RYR2, TMEM43, and TTN (excluding the following genomic regions: Chr2(GRCh37):g. 179523879-179524002 and Chr2(GRCh37):g. 179523712-179523835) genes.

 

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

 

Prior Authorization is available for this assay.

Highlights

This test includes next-generation sequencing and supplemental Sanger sequencing to evaluate the genes tested on this panel.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

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

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Arrhythmogenic Cardiomyopathy, B

Aliases
Lists additional common names for a test, as an aid in searching

Cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC)

ARVC

Arrhythmogenic right ventricular dysplasia (ARVD)

ARVD

DES

DSC2

DSG2

DSP

JUP

PKP2

RYR2

TMEM43

TTN

LMNA

Next Gen Sequencing Test

Specimen Type
Describes the specimen type validated for testing

Whole Blood EDTA

Necessary Information

1. Hereditary Cardiomyopathies and Arrhythmias: Patient Information (T725) is strongly recommended, but not required, to be filled out and sent with the specimen. This information aids in providing a more thorough interpretation of test results. Ordering providers are strongly encouraged to complete the form and send it with the specimen.

2. Include physician name and phone number with specimen.

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

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Container/Tube: Lavender top (EDTA)

Specimen Volume: 3 mL

Collection Instructions: Send specimen in original tube. Do not aliquot.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

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:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. Hereditary Cardiomyopathies and Arrhythmias: Patient Information (T725) is recommended.

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

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

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

1 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

No specimen should be rejected.

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

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

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 arrhythmogenic right ventricular cardiomyopathy (ARVC or AC)

 

Establishing a diagnosis of ARVC, 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

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 DES, DSC2, DSG2, DSP, JUP, LMNA, PKP2, RYR2, TMEM43, and TTN (excluding the following genomic regions: Chr2(GRCh37):g. 179523879-179524002 and Chr2(GRCh37):g. 179523712-179523835) genes.

 

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

 

Prior Authorization is available for this assay.

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 or AC), and left ventricular noncompaction.

 

ARVD 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 1000 to 1 in 2500. 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.

 

Table: Genes included in this 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 not previously defined: 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
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.(1) 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 arrhythmogenic right ventricular cardiomyopathy (ARVC) 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 ARVC 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 alterations (ie, 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. 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 lab upon request.

 

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.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. McNally E, MacLeod H, Dellefave-Castillo L: Arrhythmogenic right ventricular dysplasia/cardiomyopathy. In: Adam MP, Ardinger HH, Pagon RA, eds. GeneReviews [Internet]. University of Washington, Seattle; 2005. Updated May 25, 2017. 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

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

Next-generation sequencing is performed using an Illumina instrument with paired-end reads. The DNA is prepared for NGS using a custom Agilent SureSelect Target Enrichment System. Data is analyzed with a bioinformatics software pipeline. Supplemental and/or confirmatory Sanger sequencing is performed when necessary.(Unpublished Mayo method)

 

Genes analyzed: DES, DSC2, DSG2, DSP, JUP, LMNA, PKP2, RYR2, TMEM43, and TTN (excluding the following genomic regions: Chr2(GRCh37):g. 179523879-179524002 and Chr2(GRCh37):g. 179523712-179523835).

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

4 to 6 weeks after prior authorization approved

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

Extracted DNA: 2 months

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

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 US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

81439

Prior Authorization
Prior Authorization may be required by your insurance carrier.

Insurance preauthorization is available for this testing; forms are available.

 

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

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
ARVGP Arrhythmogenic Cardiomyopathy, B In Process
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
36816 Gene(s) Evaluated 48018-6
36817 Result Summary 50397-9
36818 Result Details 82939-0
36819 Interpretation 69047-9
36950 Additional Information 48767-8
36951 Method 85069-3
36952 Disclaimer 62364-5
36820 Reviewed by 18771-6

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Create a PDF

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports