Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000476602 | SCV000548768 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2023-08-04 | criteria provided, single submitter | clinical testing | Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SCN1A protein function. ClinVar contains an entry for this variant (Variation ID: 408928). This missense change has been observed in individuals with clinical features of SCN1A-related conditions (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 252 of the SCN1A protein (p.Ile252Thr). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Ile252 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15087100). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. |