Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001207242 | SCV001378586 | uncertain significance | Idiopathic generalized epilepsy; Epilepsy, idiopathic generalized, susceptibility to, 13; Epilepsy, childhood absence 4 | 2023-04-15 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 275 of the GABRA1 protein (p.Asn275Ser). 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. 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 GABRA1 protein function. ClinVar contains an entry for this variant (Variation ID: 938090). This missense change has been observed in individual(s) with clinical features of GABRA1-related conditions (PMID: 31785789). This variant is not present in population databases (gnomAD no frequency). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003331079 | SCV004038797 | uncertain significance | not specified | 2023-08-22 | criteria provided, single submitter | clinical testing | Variant summary: GABRA1 c.824A>G (p.Asn275Ser) results in a conservative amino acid change located in the Neurotransmitter-gated ion-channel transmembrane domain (IPR006029) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251184 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. De novo c.824A>G has been reported in the literature in an individual affected with Developmental Delay with multiple other de novo variants from other genes (example, Turner_2019, McRae_2016). These report(s) do not provide unequivocal conclusions about association of the variant with Developmental And Epileptic Encephalopathy, 19. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 31785789, McRae_2016 without PMID). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |