Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003781040 | SCV004569605 | pathogenic | Epilepsy, childhood absence 2; Febrile seizures, familial, 8 | 2023-11-24 | criteria provided, single submitter | clinical testing | This sequence change results in a frameshift in the GABRG2 gene (p.Tyr444Metfs*51). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 24 amino acid(s) of the GABRG2 protein and extend the protein by 26 additional amino acid residues. This variant is not present in population databases (gnomAD no frequency). This frameshift has been observed in individual(s) with GABRG2-related conditions (PMID: 23069679). It has also been observed to segregate with disease in related individuals. Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this frameshift affects GABRG2 function (PMID: 23069679). This variant disrupts a region of the GABRG2 protein in which other variant(s) (p.Asn457Tyr) have been observed in individuals with GABRG2-related conditions (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |