Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ce |
RCV000995277 | SCV001149369 | uncertain significance | not provided | 2019-01-01 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV002549904 | SCV003200693 | likely pathogenic | Epilepsy, childhood absence, susceptibility to, 1; Epilepsy, childhood absence, susceptibility to, 5 | 2022-05-28 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 288 of the GABRB3 protein (p.Thr288Ala). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GABRB3-related conditions. ClinVar contains an entry for this variant (Variation ID: 807195). 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 disrupts the p.Thr288 amino acid residue in GABRB3. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 29162865). 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. |