ClinVar Miner

Submissions for variant NM_006514.3(SCN10A):c.3674T>C (p.Ile1225Thr) (rs139638446)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000514921 SCV000610656 likely benign not provided 2017-07-05 criteria provided, single submitter clinical testing
GeneDx RCV000603074 SCV000730434 likely benign not specified 2017-12-05 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.
Invitae RCV000638724 SCV000760266 uncertain significance Brugada syndrome 2017-09-06 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 1225 of the SCN10A protein (p.Ile1225Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs139638446, ExAC 0.08%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in individuals affected with Brugada syndrome (PMID: 24998131, 27711072, 25650408) Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.

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