Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000810151 | SCV000950341 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2019-02-05 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Asp1544 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 18930999), which suggests that this may be a clinically significant amino acid residue. 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 has been observed to be de novo in an individual affected with Dravet syndrome (PMID: 21248271). This variant has also been observed to segregate with clinical features of SCN1A-related disorder in a family (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with glycine at codon 1544 of the SCN1A protein (p.Asp1544Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. |