Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000814237 | SCV000954639 | likely pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2018-12-14 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with serine at codon 1345 of the SCN1A protein (p.Pro1345Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual affected with SCN1A-related disease (PMID:28794249, 23708187). 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.Pro1345 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been observed in individuals with SCN1A-related conditions (PMID: 26993267), which suggests that this may be a clinically significant amino acid residue. 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. |
| OMIM | RCV001420538 | SCV001622841 | pathogenic | Developmental and epileptic encephalopathy 6B | 2021-05-17 | no assertion criteria provided | literature only |