ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.832C>T (p.His278Tyr)

dbSNP: rs199473562
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001842101 SCV001734896 uncertain significance Cardiac arrhythmia 2021-01-05 criteria provided, single submitter clinical testing This missense variant replaces histidine with tyrosine at codon 278 of the SCN5A protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Roden Lab, Vanderbilt University Medical Center RCV004698548 SCV005200463 uncertain significance 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, 3-38609836-G-A was evaluated for association with the loss-of-function condition Brugada Syndrome.This Variant had an AF of 0 in gnomAD v3The in silico predictor SpliceAI scored the variant as 0.3238; normal <0.2, likely damaging >0.5.Using the functional RNA-splicing assay, ParSE-seq, the variant was evaluated to have a strong negative impact on splicing (PS3_strong) following the Brnich et al. calibration framework (PMID: 31892348). In aggregate, we therefore classify this variant as VUS using these collective data.

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