ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.677C>T (p.Ala226Val)

gnomAD frequency: 0.00004  dbSNP: rs199473561
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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000454727 SCV000540294 uncertain significance not specified 2016-12-16 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: This variant has been reported in an individual with Brugada syndrome who was compound het for this and an Arg1629X variant in SCN5A. Electrophysiological experiments showed that the variant had little effect on current density alone (Tan 2015). It was identified in 3 additional patients with Brugada syndrome. This variant is present in ClinVar with no classification. It has a Max MAF of 0.18% in ExAC (9 alleles) and 0.13% in gnomAD (25 alleles). This variant is predicted to be pathogenic by prediction tools.
Labcorp Genetics (formerly Invitae), Labcorp RCV001705715 SCV000637202 likely benign not provided 2024-01-02 criteria provided, single submitter clinical testing
Mendelics RCV000987236 SCV001136486 uncertain significance Brugada syndrome 1 2019-05-28 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001144461 SCV001305060 uncertain significance Sick sinus syndrome 1 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina RCV000987236 SCV001305061 likely benign Brugada syndrome 1 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina RCV001144462 SCV001305062 benign Long QT syndrome 3 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services, Illumina RCV001144463 SCV001305063 uncertain significance Progressive familial heart block, type 1A 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina RCV001146370 SCV001307113 uncertain significance Ventricular fibrillation, paroxysmal familial, type 1 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina RCV001146371 SCV001307114 likely benign Dilated cardiomyopathy 1E 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Color Diagnostics, LLC DBA Color Health RCV001842408 SCV001345532 likely benign Cardiac arrhythmia 2018-11-18 criteria provided, single submitter clinical testing
GeneDx RCV001705715 SCV001820962 uncertain significance not provided 2022-07-19 criteria provided, single submitter clinical testing Published in vitro functional studies suggest a damaging effect (Tan et al., 2015; Ma et al., 2018); nevertheless, it is unclear how these studies may translate to a pathogenic role in vivo; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 20129283, 34649698, 24136861, 28779003, 14967853, 29728395, 30662450, 33195263, 30050137, 33071830, 25829473, 11901046)
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust RCV000058837 SCV000090357 not provided Brugada syndrome no assertion provided literature only This variant has been reported as associated with Brugada syndrome in the following publications (PMID:11901046;PMID:20129283). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute RCV000987236 SCV001433335 likely pathogenic Brugada syndrome 1 2019-03-30 flagged submission clinical testing

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