Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001876329 | SCV002117649 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2021-09-19 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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: "Benign"; Align-GVGD: "Class C0"). This missense change has been observed in individual(s) with SCN8A-related conditions (PMID: 32920374; Invitae). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with aspartic acid at codon 1523 of the SCN8A protein (p.Ala1523Asp). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and aspartic acid. |