Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001379623 | SCV001577456 | likely pathogenic | Epilepsy, childhood absence, susceptibility to, 1; Epilepsy, childhood absence, susceptibility to, 5 | 2022-02-04 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1068162). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Ser254 amino acid residue in GABRB3. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 27864847, 28053010, 30185235). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 GABRB3 protein function. This variant has not been reported in the literature in individuals affected with GABRB3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 254 of the GABRB3 protein (p.Ser254Tyr). |