ClinVar Miner

Submissions for variant NM_198903.2(GABRG2):c.1088G>A (p.Arg363Gln) (rs397514737)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187531 SCV000241125 pathogenic not provided 2016-12-01 criteria provided, single submitter clinical testing A R323Q variant that is pathogenic has been identified in the GABRG2 gene. The R323Q variant has been reported multiple times in association with epilepsy (Carvill et. al., 2013; Reinthaler et. al., 2015). Functional studies demonstrate that the R323Q variant impairs protein function (Reinthaler et. al., 2015). The R323Q variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R323Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. Therefore, the presence of R323Q is consistent with a diagnosis of a GABRG2-related disorder
Ambry Genetics RCV000720419 SCV000851296 pathogenic Seizures 2016-10-12 criteria provided, single submitter clinical testing Confirmed de novo alteration in the setting of a new disease (appropriate phenotype) in the family;Rarity in general population databases (dbsnp, esp, 1000 genomes);In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation;Deficient protein function in appropriate functional assay(s);Structural Evidence
Invitae RCV001057395 SCV001221884 pathogenic Epilepsy, childhood absence 2; Familial febrile seizures 8 2019-12-02 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 323 of the GABRG2 protein (p.Arg323Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with GABRG2-related conditions, including several de novo observations (PMID: 23708187, 27864268, 29100083, 29358611). ClinVar contains an entry for this variant (Variation ID: 60708). This variant has been reported to affect GABRG2 protein function (PMID:27864268). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000187531 SCV001247879 pathogenic not provided 2019-01-01 criteria provided, single submitter clinical testing
OMIM RCV000054505 SCV000082983 pathogenic Generalized epilepsy with febrile seizures plus 3 2013-07-01 no assertion criteria provided literature only
Bioinformatics Core,Luxembourg Center for Systems Biomedicine RCV000655995 SCV000588271 pathogenic Rolandic epilepsy 2017-01-01 no assertion criteria provided case-control CAADphred>15
OMIM RCV000767868 SCV000898480 pathogenic EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 74 2013-07-01 no assertion criteria provided literature only

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