ClinVar Miner

Submissions for variant NM_198904.4(GABRG2):c.1334G>T (p.Arg445Leu)

dbSNP: rs587780341
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000117112 SCV000151272 uncertain significance not provided 2014-03-24 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000809562 SCV000949716 pathogenic Epilepsy, childhood absence 2; Febrile seizures, familial, 8 2024-10-30 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 437 of the GABRG2 protein (p.Arg437Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of GABRG2-related conditions (internal data). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 129126). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GABRG2 protein function. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000117112 SCV001738322 uncertain significance not provided 2025-03-08 criteria provided, single submitter clinical testing Reported in a proband with epilepsy; however detailed clinical information was not provided (PMID: 39357456); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 39357456)
PreventionGenetics, part of Exact Sciences RCV004528816 SCV004104949 uncertain significance GABRG2-related disorder 2023-07-03 criteria provided, single submitter clinical testing The GABRG2 c.1310G>T variant is predicted to result in the amino acid substitution p.Arg437Leu. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.