Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000819241 | SCV000959890 | pathogenic | Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 | 2024-04-25 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 343 of the SCN2A protein (p.Asp343Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with SCN2A-related conditions (PMID: 28379373, 30928199). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 661756). 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 not expected to disrupt SCN2A protein function with a negative predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. |