ClinVar Miner

Submissions for variant NM_001127644.2(GABRA1):c.59C>T (p.Thr20Ile) (rs756553428)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000657882 SCV000779645 uncertain significance not provided 2018-05-31 criteria provided, single submitter clinical testing The T20I variant in the GABRA1 gene has been reported previously in individuals with epilepsy, however, additional clinical and familial segregation information have not been included in these studies (Klassen et al., 2011; Hernandez et al., 2016). The T20I variant is observed in 10/33,580 (0.03%) alleles from individuals of Latino background in large population cohorts (Lek et al., 2016). The T20I 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. However, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. We interpret T20I as a variant of uncertain significance.
Invitae RCV001349497 SCV001543846 uncertain significance Idiopathic generalized epilepsy; Epilepsy, juvenile myoclonic 5; Epilepsy, childhood absence 4 2020-08-06 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 20 of the GABRA1 protein (p.Thr20Ile). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs756553428, ExAC 0.03%). This variant has been observed in individual(s) with epilepsy (PMID: 21703448, 27622563). ClinVar contains an entry for this variant (Variation ID: 546090). This variant has been reported to affect GABRA1 protein function (PMID: 27622563). 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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