ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.3837C>T (p.Asp1279=)

gnomAD frequency: 0.00003  dbSNP: rs749069817
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001841935 SCV000907933 likely benign Cardiac arrhythmia 2018-10-15 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003541057 SCV001230472 uncertain significance not provided 2024-12-11 criteria provided, single submitter clinical testing This sequence change affects codon 1280 of the SCN5A mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the SCN5A protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs749069817, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with SCN5A-related conditions. ClinVar contains an entry for this variant (Variation ID: 629523). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
All of Us Research Program, National Institutes of Health RCV001841935 SCV004815813 likely benign Cardiac arrhythmia 2024-02-05 criteria provided, single submitter clinical testing
Roden Lab, Vanderbilt University Medical Center RCV004698515 SCV005200474 likely benign Brugada syndrome 1 criteria provided, single submitter research We classified this variant using data from the calibrated functional assay 'ParSE-seq' (PMID: 37732247), population data, and in silico data within the ACMG v3 framework (PMID: 25741868)The SCN5A variant, 3-38566409-G-A was evaluated for association with the loss-of-function condition Brugada Syndrome.This Variant had an AF of 0.0000263 in gnomAD v3The in silico predictor SpliceAI scored the variant as 0; normal <0.2, likely damaging >0.5.Using the functional RNA-splicing assay, ParSE-seq, the variant was evaluated to have no impact on splicing (BS3_strong) following the Brnich et al. calibration framework (PMID: 31892348). We do not apply benign splicing functional data to missense variants. In aggregate, we therefore classify this variant as LB using these collective data.
Ambry Genetics RCV004985119 SCV005500151 likely benign Cardiovascular phenotype 2024-10-30 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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