ClinVar Miner

Submissions for variant NM_000335.4(SCN5A):c.79C>T (p.Arg27Cys) (rs746360906)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000552525 SCV000637205 uncertain significance Brugada syndrome 2018-06-19 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 27 of the SCN5A protein (p.Arg27Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs746360906, ExAC 0.005%). This variant has not been reported in the literature in individuals with SCN5A-related disease. ClinVar contains an entry for this variant (Variation ID: 463358). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). 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.
Stanford Center for Inherited Cardiovascular Disease,Stanford University RCV000786216 SCV000924944 uncertain significance not provided 2017-11-01 no assertion criteria provided provider interpretation p.Arg27Cys (c.79C>T) in exon 2 of the SCN5A gene (NM_198056.2; chr3-38674720-G-A) SCICD Classification: variant of uncertain significance, likely benign based on lack of case data and frequency in the general population. We do not feel it is suitable for assessing risk in healthy relatives ("predictive genetic testing"). Case data (not including our patient): none available per our searches and lab report. Population data: Highest MAF in South Asian population: 0.003249%. The variant was reported online in 4 of 122888 individuals in the Genome Aggregation Consortium Dataset (gnomAD; http://gnomad.broadinstitute.org/), which currently includes variant calls on >140,000 unrelated individuals of African, Asian, European, Ashkenazi, Latino descent. The phenotype of those individuals is not publicly available. The dataset is comprised of multiple cohorts, some of which were recruited from the general population, others were enriched for common cardiovascular disease.

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