ClinVar Miner

Submissions for variant NM_006009.4(TUBA1A):c.1264C>T (p.Arg422Cys) (rs137853049)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000622854 SCV000742037 pathogenic Inborn genetic diseases 2016-12-04 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: POSITIVE: Relevant Alteration(s) Detected
GeneDx RCV000432377 SCV000520890 pathogenic not provided 2018-08-30 criteria provided, single submitter clinical testing The R422C variant in the TUBA1A gene has been reported previously as a de novo variant in one individual with lissencephaly and clinical features including spastic diplegia, speech delay, perisylvian pachygyria, mild corpus callosum hypoplasia, and mild vermian hypoplasia (Bahi-Buisson et al., 2008). The R422C variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R422C variant is a non-conservative amino acid substitution and occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. A missense variant at the same residue (R422H) has been reported in the Human Gene Mutation Database in association with lissencephaly (Stenson et al., 2014), supporting the functional importance of this region of the protein. We interpret R422C as a pathogenic variant.
Institute of Human Genetics,Friedrich-Alexander-Universität Erlangen-Nürnberg RCV000767469 SCV000898084 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 54 months old born individual of female sex. The c.1264C>T, p.(Arg422Cys) variant has been reported as a variant of de novo origin. This variant and associated phenotype was previously reported by Bahi-Buisson et al. J Med Genet, 2008 PMID: 18728072. HPO-standardized clinical features were: Hypoplasia of the corpus callosum (HP:0002079); Pachygyria (HP:0001302); Cerebellar vermis hypoplasia (HP:0001320); Abnormality of the internal capsule (HP:0012502); Microcephaly (HP:0000252); Spasticity (HP:0001257); no Seizures (-HP:0001250)
OMIM RCV000007492 SCV000027692 pathogenic Lissencephaly 3 2008-10-01 no assertion criteria provided literature only

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