ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.5318C>A (p.Ser1773Tyr) (rs121917951)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000471658 SCV000548776 likely pathogenic Early infantile epileptic encephalopathy 2018-09-21 criteria provided, single submitter clinical testing This sequence change replaces serine with tyrosine at codon 1773 of the SCN1A protein (p.Ser1773Tyr). The serine residue is highly conserved and there is a large physicochemical difference between serine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with clinical features of epileptic encephalopathy, in at least one of whom it was found de novo (PMID: 29100083, Invitae). 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: "Probably Damaging"; Align-GVGD: "Class C15"). This variant disrupts the p.Ser1773 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 17054684), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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