ClinVar Miner

Submissions for variant NM_198903.2(GABRG2):c.1207C>T (p.Arg403Trp) (rs374512652)

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
GeneDx RCV000187534 SCV000241128 uncertain significance not provided 2017-08-09 criteria provided, single submitter clinical testing p.Arg363Trp (CGG>TGG):c.1087 C>T in exon 8 of the GABRG2 gene (NM_000816.3) The R363W variant has been reported previously in an unaffected control individual; however, additional information regarding the variant or the phenotype of the individual was not reported (Reinthaler et al., 2015). A different amino acid substitution at this position (R363Q) has been reported in an individual with generalized epilepsy with febrile seizures plus (GEFS+); however, additional clinical information was not provided, and parental studies were not performed (Cantarín-Extremera et al. 2011). The R363W variant is observed in 2/10406 (0.2%) alleles from individuals of African background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R363W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Ambry Genetics RCV000720807 SCV000851691 uncertain significance Seizures 2017-05-23 criteria provided, single submitter clinical testing The p.R363W variant (also known as c.1087C>T), located in coding exon 8 of the GABRG2 gene, results from a C to T substitution at nucleotide position 1087. The arginine at codon 363 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV000795577 SCV000935045 uncertain significance Epilepsy, childhood absence 2; Familial febrile seizures 8 2019-10-08 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 363 of the GABRG2 protein (p.Arg363Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs374512652, ExAC 0.02%). This variant has been observed in one or more individuals who were not affected with seizures (Invitae). ClinVar contains an entry for this variant (Variation ID: 205552). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C1). 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. 5
CeGaT Praxis fuer Humangenetik Tuebingen RCV000187534 SCV001154583 uncertain significance not provided 2019-08-01 criteria provided, single submitter clinical testing

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.