Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001217542 | SCV001389388 | likely pathogenic | Epilepsy, childhood absence 2; Febrile seizures, familial, 8 | 2024-01-10 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 323 of the GABRG2 protein (p.Arg323Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with GABRG2-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 946639). 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 GABRG2 protein function with a positive predictive value of 95%. This variant disrupts the p.Arg323 amino acid residue in GABRG2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23708187, 27334371, 27864268, 29100083). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |