ClinVar Miner

Submissions for variant NM_198903.2(GABRG2):c.868G>A (p.Glu290Lys) (rs549251133)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521260 SCV000619048 uncertain significance not provided 2017-07-17 criteria provided, single submitter clinical testing The E250K variant in the GABRG2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The E250K variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The E250K 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 not conserved. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret E250K as a variant of uncertain significance.
Invitae RCV001064372 SCV001229269 uncertain significance Epilepsy, childhood absence 2; Familial febrile seizures 8 2020-10-01 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 250 of the GABRG2 protein (p.Glu250Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. 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 conditions. ClinVar contains an entry for this variant (Variation ID: 450459). 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: Tolerated; 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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