ClinVar Miner

Submissions for variant NM_198903.2(GABRG2):c.1120G>A (p.Ala374Thr) (rs398123523)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000518838 SCV000111189 uncertain significance not provided 2013-08-09 criteria provided, single submitter clinical testing
GeneDx RCV000518838 SCV000515993 likely pathogenic not provided 2017-07-18 criteria provided, single submitter clinical testing Although the A334T variant has not been published, this variant has been detected in several unrelated individuals who were referred for epilepsy genetic testing at GeneDx, and it segregated with seizures in immediate relatives in some families; however, segregation data is limited at this time. The A334T variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The A334T variant is a non-conservative amino acid substitution that occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Based on the currently available information, we interpret A334T as a likely pathogenic variant.
Invitae RCV000797789 SCV000937368 uncertain significance Epilepsy, childhood absence 2; Familial febrile seizures 8 2020-05-26 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 334 of the GABRG2 protein (p.Ala334Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with GABRG2-related disease. ClinVar contains an entry for this variant (Variation ID: 93433). 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: Possibly Damaging; Align-GVGD: Class C0). 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.

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