Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| New York Genome Center | RCV002266660 | SCV002548703 | uncertain significance | Epilepsy, childhood absence, susceptibility to, 5; Developmental and epileptic encephalopathy, 43 | 2021-08-12 | criteria provided, single submitter | clinical testing | The inherited heterozygous c.424C>T (p.Arg142Cys) missense variant identified in the GABRB3 gene has not been reported in affected individuals in the literature. The variant is absent from gnomAD(v3) database suggesting it is not a common benign variant in the populations represented in that database. The variant affects an evolutionarily conserved residue and is predicted deleterious by multiple in silico prediction tools (CADD score = 34, REVEL score =0.906). Given the lack of functional studies, the inherited heterozygous c.424C>T (p.Arg142Cys) missense variant identified in the GABRB3 gene is reported as a Variant of Uncertain Significance. |
| Labcorp Genetics |
RCV003774848 | SCV004588259 | uncertain significance | Epilepsy, childhood absence, susceptibility to, 1; Epilepsy, childhood absence, susceptibility to, 5 | 2023-10-05 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 142 of the GABRB3 protein (p.Arg142Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of early infantile epileptic encephalopathy (Invitae). ClinVar contains an entry for this variant (Variation ID: 1696530). 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.Arg142 amino acid residue in GABRB3. Other variant(s) that disrupt this residue have been observed in individuals with GABRB3-related conditions (PMID: 28053010), which suggests that this may be a clinically significant amino acid residue. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |