ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.2624C>G (p.Thr875Arg)

dbSNP: rs121918623
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001035614 SCV001198948 uncertain significance Early infantile epileptic encephalopathy with suppression bursts 2019-11-19 criteria provided, single submitter clinical testing This sequence change replaces threonine with arginine at codon 875 of the SCN1A protein (p.Thr875Arg). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SCN1A-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Thr875 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10742094, 12086636, 11567038, 14702334). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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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