ClinVar Miner

Submissions for variant NM_006009.4(TUBA1A):c.424G>T (p.Gly142Cys) (rs1555162407)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000497965 SCV000589375 likely pathogenic not provided 2017-04-10 criteria provided, single submitter clinical testing A variant that is likely pathogenic has been identified in the TUBA1A gene. The G142C variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The G142C variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The G142C 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 alters a highly conserved position in the predicted GTP binding domain of the TUBA1A protein. A missense variant in a nearby residue (V137D) has been reported in association with lissencephaly with cerebellar hypoplasia; however, the clinical significance of the V137D change is unknown as parental studies were not performed (Kumar et al, 2010). In silico analysis predicts the G142C variant is probably damaging to the protein structure/function. Additionally, targeted parental testing indicates this variant is apparently de novo. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Institute of Human Genetics,Friedrich-Alexander-Universität Erlangen-Nürnberg RCV000767511 SCV000898126 likely pathogenic Tubulinopathies 2018-07-01 criteria provided, single submitter literature only A variant that is classified as likely pathogenic has been identified in the TUBA1A gene in a born individual of unknown sex. The c.424G>T, p.(Gly142Cys) variant has been reported as a variant of germline/unknown origin.

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