ClinVar Miner

Submissions for variant NM_000814.6(GABRB3):c.239T>C (p.Met80Thr)

dbSNP: rs1064794797
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000478028 SCV000569958 likely pathogenic not provided 2016-04-07 criteria provided, single submitter clinical testing The M80T variant in the GABRB3 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The M80T variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The M80T 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. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret M80T as a strong candidate for a pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV000822033 SCV000962813 uncertain significance Epilepsy, childhood absence, susceptibility to, 1; Epilepsy, childhood absence, susceptibility to, 5 2018-11-03 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with GABRB3-related disease. ClinVar contains an entry for this variant (Variation ID: 420927). This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with threonine at codon 80 of the GABRB3 protein (p.Met80Thr). The methionine residue is moderately conserved and there is a moderate physicochemical difference between methionine and threonine.

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