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 2020-02-13 criteria provided, single submitter clinical testing Published functional studies demonstrate impaired protein function (Reinthaler et. al., 2015; Absalom et al., 2019) This variant is associated with the following publications: (PMID: 28714951, 25730860, 28351718, 30728247, 31087664, 28191890, 23708187, 25726841, 27864268, 27334371, 29720203, 29358611, 31139143, 29100083)
Ambry Genetics RCV000720419 SCV000851296 pathogenic Seizures 2016-10-12 criteria provided, single submitter clinical testing The p.R323Q pathogenic mutation (also known as c.968G>A), located in coding exon 8 of the GABRG2 gene, results from a G to A substitution at nucleotide position 968. The arginine at codon 323 is replaced by glutamine, an amino acid with highly similar properties. This alteration has been determined to be the result of a de novo mutation in two patients with epileptic encephalopathies (Carvill GL et al. Nat. Genet., 2013 Jul;45:825-30; Reinthaler EM et al. Ann. Neurol., 2015 Jun;77:972-86). Electrophysiology functional studies indicate this variant results in altered GABA<sub>A</sub>-R chloride channel kinetics (Reinthaler EM et al. Ann. Neurol., 2015 Jun;77:972-86). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Invitae RCV001057395 SCV001221884 pathogenic Epilepsy, childhood absence 2; Familial febrile seizures 8 2020-10-16 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 RCV001268930 SCV001448180 pathogenic Developmental and epileptic encephalopathy, 74 2013-07-01 no assertion criteria provided literature only

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