Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000700072 | SCV000828811 | uncertain significance | Early infantile epileptic encephalopathy with suppression bursts | 2018-04-06 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine with leucine at codon 1263 of the SCN1A protein (p.Phe1263Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SCN1A-related disease. However, a different variant (c.3789C>G) giving rise to the same protein effect observed here (p.Phe1263Leu) has been reported in an individual affected with severe myoclonic epilepsy in infancy (PMID: 12566275). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant identified in the SCN1A gene is located in the transmembrane spanning D3-S2 region of the resulting protein (PMID: 25348405, 18804930), but it is unclear how this variant impacts the function of this protein. |
| Revvity Omics, |
RCV003140110 | SCV003820725 | likely pathogenic | not provided | 2023-04-04 | criteria provided, single submitter | clinical testing |