ClinVar Miner

Submissions for variant NM_006920.6(SCN1A):c.5285C>T (p.Ser1762Phe) (rs121917951)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000693267 SCV000821128 likely pathogenic Early infantile epileptic encephalopathy 2018-05-18 criteria provided, single submitter clinical testing This sequence change replaces serine with phenylalanine at codon 1773 of the SCN1A protein (p.Ser1773Phe). The serine residue is highly conserved and there is a large physicochemical difference between serine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual affected with severe myoclonic epilepsy of infancy (SMEI) (PMID: 17054684). ClinVar contains an entry for this variant (Variation ID: 68568). This variant identified in the SCN1A gene is located in the extracellular D4-S5/S6 region of the resulting protein (PMID: 25348405, 18804930), but it is unclear how this variant impacts the function of this protein. 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 C15"). The p.Ser1773 amino acid residue in SCN1A has been determined to be clinically significant (Invitae). This suggests that variants that disrupt this residue are likely to be causative of disease. 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.
UniProtKB/Swiss-Prot RCV000059443 SCV000090968 not provided Severe myoclonic epilepsy in infancy no assertion provided not provided

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