Providing a genetic evaluation for patients with a personal or family history suggestive of Brugada syndrome
Establishing a diagnosis of a BrS, in some cases, allowing for appropriate management and surveillance for disease features based on the gene involved
Identifying variants within genes known to be associated with increased risk for disease features and allowing for predictive testing of at-risk family members
This test uses next generation sequencing to test for variants in the CACNA1C, CACNA2D1, GPD1L, KCNE3, KCNJ8, SCN3B, CACNB2, SCN1B, and SCN5A genes.
This test may aid in the diagnosis of Brugada syndrome.
Identification of a pathogenic variant may assist with prognosis, clinical management, familial screening, and genetic counseling.
Prior Authorization is available for this assay; see Special Instructions.
This test includes next-generation sequencing and supplemental Sanger sequencing to evaluate the genes tested on this panel.
Custom Sequence Capture and Targeted Next Generation Sequencing Followed by Polymerase Chain Reaction (PCR) and Supplemental Sanger Sequencing
Brugada syndrome
BRS
CACNA1C
CACNA2D1
GPD1L
KCNE3
KCNJ8
SCN3B
CACNB2
SCN1B
SCN5A
Next Gen Sequencing Test
Whole Blood EDTA
Targeted testing for familial variants (also called site-specific or known mutations testing) is available for the genes on this panel. See FMTT / Familial Mutation, Targeted Testing, Varies.
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 assay; see Special Instructions. 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 in Special Instructions:
-Informed Consent for Genetic Testing (T576)
-Informed Consent for Genetic Testing-Spanish (T826)
2. Brugada Syndrome Multi-Gene Panel Prior Authorization Ordering Instructions in Special Instructions
3. Hereditary Cardiomyopathies and Arrhythmias: Patient Information (T725) is recommended. See Special Instructions.
4. If not ordering electronically, complete, print, and send a Cardiovascular Test Request (T724) with the specimen.
1 mL
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Whole Blood EDTA | Ambient (preferred) | ||
Refrigerated |
Providing a genetic evaluation for patients with a personal or family history suggestive of Brugada syndrome
Establishing a diagnosis of a BrS, in some cases, allowing for appropriate management and surveillance for disease features based on the gene involved
Identifying variants within genes known to be associated with increased risk for disease features and allowing for predictive testing of at-risk family members
This test uses next generation sequencing to test for variants in the CACNA1C, CACNA2D1, GPD1L, KCNE3, KCNJ8, SCN3B, CACNB2, SCN1B, and SCN5A genes.
This test may aid in the diagnosis of Brugada syndrome.
Identification of a pathogenic variant may assist with prognosis, clinical management, familial screening, and genetic counseling.
Prior Authorization is available for this assay; see Special Instructions.
Brugada syndrome (BrS) is a genetic cardiac disorder characterized by ST segment elevation in leads V1-V3 on electrocardiography (EKG) with a high risk for ventricular arrhythmias, which can lead to sudden cardiac death. BrS is inherited in an autosomal dominant manner and is caused by pathogenic variants in genes that encode cardiac ion channels. The diagnosis of BrS is established based on the characteristic EKG abnormality along with personal and family health history, and requires exclusion of other causes including cardiac structural abnormalities, medications, and electrolyte imbalances.
BrS has also been called sudden unexplained nocturnal death syndrome (SUNDS) due to the tendency for syncope and sudden cardiac death to occur at rest or during sleep. The most common presentation of BrS is a male in his 40s with a history of syncopal episodes and malignant arrhythmias. However, presentation may occur at any age including infancy, where BrS may present as sudden infant death syndrome. Published studies indicate that BrS is responsible for 4% to 12% of unexpected sudden deaths and for up to 20% of all sudden death in individuals with a structurally normal heart.
The prevalence of BrS in the general population is difficult to determine due to the challenges of diagnosing the condition. In Southeast Asia where SUNDS is endemic, the prevalence of BrS is estimated to be 1 in 2000. Of note, men are 8 to 10 times more likely to express symptoms of BrS, but the disease affects females as well and both sexes are at risk for ventricular arrhythmia and sudden death.
Approximately 25% to 30% of BrS is accounted for by pathogenic variants in the genes known to cause the disorder, with the majority of cases attributed to the SCN5A gene. Although the majority of pathogenic variants identified to date have been detected by sequence analysis, large deletions in the SCN5A, SCN3B, CACNA1C, and KCNE3 genes have been reported in BrS. Genetic testing for BrS is supported by multiple consensus statements to confirm the diagnosis and identify at-risk family members. This is particularly important because the majority of patients with BrS are asymptomatic, but asymptomatic individuals may still be at increased risk for cardiac events. Pre- and post-test genetic counseling is an important factor in the diagnosis and management of BrS and is supported by expert consensus statements.
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 Brugada syndrome (BrS) 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 BrS 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 lab 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. Brugada R, Campuzano O, Sarquella-Brugada G, Brugada P, Brugada J, Hong K: Brugada syndrome. In: Adam MP, Ardinger HH, Pagon RA, et al eds. GeneReviews [Internet]. eds. University of Washington, Seattle; 2005. Updated November 17, 2016. Accessed June 2018. Available at www.ncbi.nlm.nih.gov/books/NBK1517/
3. Priori SG, Wilde AA, Horie M, et al: HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes. Heart Rhythm. 2013;10:12:1932-1963
4. 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
5. Neilsen MW, Holst AG, Olesen SP, Olesen MS: The genetic component of Brugada syndrome. Front Physiol. 2013;4:179:1-11
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 confirmatory Sanger sequencing are performed when necessary.(Unpublished Mayo method)
Genes analyzed: CACNA1C, CACNA2D1, GPD1L, KCNE3, KCNJ8, SCN3B, CACNB2, SCN1B, and SCN5A.
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.
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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 Clinic Laboratories will receive information on eligibility and how to apply.
Test Id | Test Order Name | Order LOINC Value |
---|---|---|
BRGGP | Brugada Syndrome Multi-Gene 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.
|
---|---|---|
36831 | Gene(s) Evaluated | 48018-6 |
36832 | Result Summary | 50397-9 |
36833 | Result Details | 82939-0 |
36834 | Interpretation | 69047-9 |
36959 | Additional Information | 48767-8 |
36960 | Method | 85069-3 |
36961 | Disclaimer | 62364-5 |
36835 | Reviewed by | 18771-6 |