Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Human Genetics, |
RCV002286479 | SCV002576433 | uncertain significance | Developmental and epileptic encephalopathy, 11 | 2022-08-23 | criteria provided, single submitter | clinical testing | Criteria applied: PS2_MOD, PP2, PP3 |
Labcorp Genetics |
RCV003774946 | SCV004604149 | pathogenic | Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 | 2023-08-22 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 733 of the SCN2A protein (p.Ala733Thr). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with SCN2A-related conditions (PMID: 28379373). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 1707519). 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 SCN2A protein function. For these reasons, this variant has been classified as Pathogenic. |