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
This test uses Sanger sequencing to test for variants in certain exons of the following genes:
MYH6 exon 26
MYH7 exon 27
Identification of a pathogenic variant may assist with prognosis, clinical management, familial screening, and genetic counseling.
Prior Authorization is available for this assay.
Custom Sequence Capture and Targeted Next-Generation Sequencing followed by Polymerase Chain Reaction (PCR) and supplemental Sanger Sequencing
Cardiomyopathy
Dilated Cardiomyopathy (DCM)
DCM
ABCC9
ACTC1
ACTN2
ANKRD1
CRYAB
CSRP3
DES
LAMA4
LAMP2
LDB3
LMNA
MYBPC3
MYH6
MYH7
MYPN
NEXN
PLN
RAF1
RBM20
SCN5A
SGCD
TAZ
TCAP
TNNC1
TNNI3
TNNT2
TPM1
TTN
TTR
VCL
Next Gen Sequencing Test
Whole Blood EDTA
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.
Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.
Container/Tube: Lavender top (EDTA)
Specimen Volume: 3 mL
Collection Instructions: Send specimen in original tube. Do not aliquot.
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. Dilated Cardiomyopathy Multi-Gene Panel Prior Authorization Ordering Instructions
3. Hereditary Cardiomyopathies and Arrhythmias: Patient Information (T725) is recommended
4. If not ordering electronically, complete, print, and send a Cardiovascular Test Request Form (T724) with the specimen.
1 mL
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Whole Blood EDTA | Ambient (preferred) | ||
Refrigerated |
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
This test uses Sanger sequencing to test for variants in certain exons of the following genes:
MYH6 exon 26
MYH7 exon 27
Identification of a pathogenic variant may assist with prognosis, clinical management, familial screening, and genetic counseling.
Prior Authorization is available for this assay.
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, dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy, and left ventricular noncompaction.
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 DCM.
The majority of familial DCM 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 this 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)
An interpretive report will be provided.
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.
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 a hereditary dilated cardiomyopathy (DMC) 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 hereditary DMC 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, less than 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 laboratory upon request.
Contact the laboratory if additional information is required regarding the transcript or human genome assembly used for the analysis of this patient's results.
2. Hershberger RE, Morales A: Dilated cardiomyopathy overview. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2007. Updated July 29, 2021. Accessed September 21, 2021. Available at www.ncbi.nlm.nih.gov/books/NBK1309/
3. 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
4. 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
5. Herman DS, Lam L, Taylor MR, et al: Truncations of titin causing dilated cardiomyopathy. N Engl J Med. 2012;366(7):619-628
6. Dhandapany PS, Razzaque MA, Muthusami U, et al: RAF1 mutations in childhood-onset dilated cardiomyopathy. Nat Genet. 2014;46(6):635-639
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
Next-generation sequencing (NGS) 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)
The following genes are evaluated in this multigene panel: ABCC9, ACTC1, ACTN2, ANKRD1, CRYAB, CSRP3, DES, LAMA4, LAMP2, LDB3, LMNA, MYBPC3, MYH6, MYH7, MYPN, NEXN, PLN, RAF1, RBM20, SCN5A, SGCD, TAZ, TCAP, TNNC1, TNNI3, TNNT2, TPM1, TTN (excluding the following genomic regions: Chr2(GRCh37):g. 179523879-179524002 and Chr2(GRCh37):g. 179523712-179523835), TTR, and VCL.
Monday
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.
81439
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.
Test Id | Test Order Name |
Order LOINC Value
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.
|
---|---|---|
DCMGP | Dilated Cardiomyopathy Panel, 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.
|
---|---|---|
36811 | Gene(s) Evaluated | 48018-6 |
36812 | Result Summary | 50397-9 |
36813 | Result Details | 82939-0 |
36814 | Interpretation | 69047-9 |
36947 | Additional Information | 48767-8 |
36948 | Method | 85069-3 |
36949 | Disclaimer | 62364-5 |
36815 | Reviewed by | 18771-6 |