ClinVar Miner

Submissions for variant NM_006009.4(TUBA1A):c.1226T>C (p.Val409Ala) (rs797045005)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000492850 SCV000583013 likely pathogenic not provided 2018-03-29 criteria provided, single submitter clinical testing A variant that is likely pathogenic has been identified in the TUBA1A gene. The V409A variant has been reported previously as a de novo variant in a pregnancy with severe lissencephaly and cerebellar hypoplasia; however, functional characterization of the variant was not completed (Bahi-Buisson et al., 2014). The V409A variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The V409A variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, 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. Furthermore, a missense variant in the same residue (V409I) has been reported in association with a TUBA1A-related disorder (Bahi-Buisson et al., 2014). 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 RCV000767496 SCV000898111 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 32 gestational week old fetal individual of male sex. The c.1226T>C, p.(Val409Ala) variant has been reported as a variant of de novo origin. This variant and associated phenotype was previously reported by Bahi-Buisson et al. Brain, 2014 PMID: 24860126. HPO-standardized clinical features were: Agenesis of the corpus callosum (HP:0001274); Agyria-pachygyria (HP:0031883, HP:0001302); Cerebellar vermis hypoplasia (HP:0001320); Hypoplasia of the brainstem (HP:0002365); Cerebellar hypoplasia (HP:0001321); no Congenital microcephaly (-HP:0011451)
Mendelics RCV000190503 SCV000245389 pathogenic Lissencephaly 3 2014-07-01 no assertion criteria provided clinical testing

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