ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.2355G>A (p.Met785Ile)

dbSNP: rs2105827770
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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 RCV001377649 SCV001575032 likely pathogenic Early infantile epileptic encephalopathy with suppression bursts 2020-05-21 criteria provided, single submitter clinical testing 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. This variant disrupts the p.Met785 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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 C0"). This variant has been observed in individual(s) with Dravet syndrome (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with isoleucine at codon 785 of the SCN1A protein (p.Met785Ile). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and isoleucine.

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