Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001054726 | SCV001219075 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2020-09-07 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with lysine at codon 954 of the SCN1A protein (p.Glu954Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with classic Dravet syndrome or severe myoclonic epilepsy of infancy (PMID: 20110217, 21248271). ClinVar contains an entry for this variant (Variation ID: 68606). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Glu954 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been observed in individuals with SCN1A-related conditions (Invitae), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic. |
Uni |
RCV000059483 | SCV000091008 | not provided | Severe myoclonic epilepsy in infancy | no assertion provided | not provided |