ClinVar Miner

Submissions for variant NM_001127644.2(GABRA1):c.1234A>T (p.Thr412Ser) (rs1229633395)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000519418 SCV000621878 uncertain significance not provided 2017-10-23 criteria provided, single submitter clinical testing The T412S variant in the GABRA1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The T412S variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The T412S variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. While this substitution occurs at a position that is conserved across species, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret T412S as a variant of uncertain significance.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000519418 SCV001154578 uncertain significance not provided 2016-06-01 criteria provided, single submitter clinical testing
Invitae RCV001325329 SCV001516320 uncertain significance Idiopathic generalized epilepsy; Epilepsy, juvenile myoclonic 5; Epilepsy, childhood absence 4 2020-03-26 criteria provided, single submitter clinical testing This sequence change replaces threonine with serine at codon 412 of the GABRA1 protein (p.Thr412Ser). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with GABRA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 453024). 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: Probably 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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