ClinVar Miner

Submissions for variant NM_006009.4(TUBA1A):c.1265G>A (p.Arg422His) (rs137853050)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255074 SCV000321986 pathogenic not provided 2018-06-25 criteria provided, single submitter clinical testing The R422H pathogenic variant in the TUBA1A gene has been reported previously as a de novo variant in an multiple individuals with lissencephaly and associated brain abnormalities (Bahi-Buisson et al., 2008, Morris-Rosendahl et al., 2008). A different missense variant at the same residue (R422C) has also been reported in association with a TUBA1A-related disorder (Bahi-Buisson et al., 2008). The R422H substitution was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Therefore, we interpret R422H to be a pathogenic variant.
GeneReviews RCV000007493 SCV000266414 pathogenic Lissencephaly 3 2015-12-04 no assertion criteria provided literature only Classic lissencephaly
Genetic Services Laboratory, University of Chicago RCV000007493 SCV000195272 pathogenic Lissencephaly 3 2013-02-08 criteria provided, single submitter clinical testing
Institute of Human Genetics,Friedrich-Alexander-Universität Erlangen-Nürnberg RCV000767410 SCV000898025 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 9 years old born individual of male sex. The c.1265G>A, p.(Arg422His) variant has been reported as a variant of de novo origin. This variant and associated phenotype was previously reported by Morris-Rosendahl et al. Clin Genet, 2008 PMID: 18954413. HPO-standardized clinical features were: Partial agenesis of the corpus callosum (HP:0001338); Pachygyria (HP:0001302); Cerebellar vermis hypoplasia (HP:0001320); Hypoplasia of the pons (HP:0012110); Dysgenesis of the hippocampus (HP:0025101); Dilation of lateral ventricles, Dilated fourth ventricle (HP:0006956, HP:0002198); Gray matter heterotopia (HP:0002281); Congenital microcephaly (HP:0011451); Microcephaly (HP:0000252); Muscular hypotonia (HP:0001252); Generalized tonic-clonic seizures (HP:0002069)
OMIM RCV000007493 SCV000027693 pathogenic Lissencephaly 3 2008-11-01 no assertion criteria provided literature only

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