ClinVar Miner

Submissions for variant NM_000335.4(SCN5A):c.856G>T (p.Ala286Ser) (rs61746118)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000618432 SCV000737395 likely benign Cardiovascular phenotype 2016-06-02 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Subpopulation frequency in support of benign classification,In silico models in agreement (benign)
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058852 SCV000090372 not provided not provided no assertion provided literature only This variant has been reported in the following publications (PMID:19841300;PMID:20129283).
GeneDx RCV000154846 SCV000235293 likely benign not specified 2017-05-31 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Integrated Genetics/Laboratory Corporation of America RCV000154846 SCV000918196 likely benign not specified 2018-09-17 criteria provided, single submitter clinical testing Variant summary: SCN5A c.856G>T (p.Ala286Ser) results in a conservative amino acid change located in the Ion transport domain (IPR005821) of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00029 in 279948 control chromosomes, predominantly within the African subpopulation, at a frequency of 0.0029, in the gnomAD database. The observed variant frequency within African control individuals in the gnomAD database is approximately 29-fold of the estimated maximal expected allele frequency for a pathogenic variant in SCN5A causing Arrhythmia phenotype (0.0001), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. To our knowledge, no occurrence of c.856G>T in individuals affected with Arrhythmia and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Invitae RCV000227077 SCV000291836 likely benign Brugada syndrome 2018-01-22 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000154846 SCV000204528 likely benign not specified 2018-04-10 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory

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