Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001380063 | SCV001577998 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2020-09-20 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Val1315 amino acid residue in SCN8A. 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 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 SCN8A-related conditions (PMID: 26993267, 29432985, 31026061). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with methionine at codon 1315 of the SCN8A protein (p.Val1315Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. |
| Division of Genomic Medicine, |
RCV003330327 | SCV004037451 | pathogenic | Developmental and epileptic encephalopathy, 13 | 2023-10-01 | criteria provided, single submitter | clinical testing | This missense variant was found in a patient with epileptic encephalopathy (PP4), absent from controls (PM2) and assumed de novo (PM6). Also, multiple lines of computational evidence support a deleterious effect (PP3), and reported as pathogenic by others (PS1). It is judged to be pathogenic according to ACMG Guidelines, 2015. |