ClinVar Miner

Submissions for variant NM_198903.2(GABRG2):c.1276C>T (p.Pro426Ser) (rs757311213)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000766325 SCV000573211 uncertain significance not provided 2017-02-13 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the GABRG2 gene. The P378S variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The P378S variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P378S 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 across species. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is 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.
Athena Diagnostics Inc RCV000483452 SCV000613372 uncertain significance not specified 2017-01-13 criteria provided, single submitter clinical testing
Invitae RCV001219636 SCV001391584 uncertain significance Epilepsy, childhood absence 2; Familial febrile seizures 8 2020-07-15 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 378 of the GABRG2 protein (p.Pro378Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. This variant is present in population databases (rs757311213, ExAC 0.001%). This variant has not been reported in the literature in individuals with GABRG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 423505). 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: Benign; 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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