Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Bioinformatics, |
RCV000180797 | SCV000221752 | pathogenic | Severe myoclonic epilepsy in infancy | 2014-12-20 | criteria provided, single submitter | research | |
Invitae | RCV002517630 | SCV003524842 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2022-04-28 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1451 of the SCN1A protein (p.Pro1451Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with SCN1A-related conditions (PMID: 25754450, 26096185). ClinVar contains an entry for this variant (Variation ID: 189843). 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. This variant disrupts the p.Pro1451 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17054684; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |