Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001051151 | SCV001215291 | likely pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2020-05-04 | criteria provided, single submitter | clinical testing | This variant has been observed in individual(s) with clinical features of early infantile epileptic encephalopathy (Invitae). In at least one individual the variant was observed to be de novo. 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. 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 is not present in population databases (ExAC no frequency). This sequence change replaces methionine with isoleucine at codon 255 of the SCN8A protein (p.Met255Ile). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and isoleucine. |