ClinVar Miner

Submissions for variant NM_006009.4(TUBA1A):c.190C>T (p.Arg64Trp) (rs1064794568)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000486860 SCV000569468 pathogenic not provided 2017-02-21 criteria provided, single submitter clinical testing The R64W variant in the TUBA1A gene has been reported previously as a de novo change in an individual with thin cerebral parenchyma, agenesis of the cerebellum and corpus callosum, hypoplastic brain stem, focal seizures, and spastic tetraplegia (Yokoi et al., 2015). Functional studies suggest that R64W impairs microtubule stability (Yokoi et al., 2015). The R64W variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R64W 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, and in silico analysis predicts this variant is probably damaging to the protein structure/function.
Institute of Human Genetics,Friedrich-Alexander-Universität Erlangen-Nürnberg RCV000767424 SCV000898039 pathogenic Tubulinopathies 2018-07-01 criteria provided, single submitter literature only A variant that is classified as pathogenic has been identified in the TUBA1A gene in a 3 years old born individual of female sex. The c.190C>T, p.(Arg64Trp) variant has been reported as a variant of de novo origin. This variant and associated phenotype was previously reported by Yokoi et al. Sci Rep, 2015 PMID: 26493046. HPO-standardized clinical features were: Agenesis of the corpus callosum (HP:0001274); Other (NA); Hypoplasia of the brainstem (HP:0002365); Cerebellar agenesis (HP:0012642); Dilation of lateral ventricles (HP:0006956); Congenital microcephaly (HP:0011451); Spasticity, muscular hypotonia (HP:0001257, HP:0001252); Focal seizures (HP:0007359); Optic nerve hypoplasia (HP:0000609)

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