Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000636373 | SCV000757812 | uncertain significance | Early infantile epileptic encephalopathy with suppression bursts | 2021-05-22 | criteria provided, single submitter | clinical testing | 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 D3-D6 region of the resulting protein (PMID: 25348405, 18804930), but it is unclear how this variant impacts the function of this protein. 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: "Possibly Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals with SCN1A-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with valine at codon 1459 of the SCN1A protein (p.Met1459Val). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and valine. |