ClinVar Miner

Submissions for variant NM_006009.4(TUBA1A):c.1096G>A (p.Gly366Arg) (rs1555162299)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000522300 SCV000617361 likely pathogenic not provided 2017-06-28 criteria provided, single submitter clinical testing A variant that is likely pathogenic has been identified in the TUBA1A gene. The G366R variant has been reported previously as a de novo variant in an individual with lissencephaly; however, functional characterization of the variant was not completed (Okumura et al., 2013). The G366R variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The G366R 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. Furthermore, missense variants in nearby residues (A369T, V371E) have been reported in the Human Gene Mutation Database in association with TUBA1A-related disorders (Stenson 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 RCV000767417 SCV000898032 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 2 months old born individual of female sex. The c.1096G>A, p.(Gly366Arg) variant has been reported as a variant of de novo origin. This variant and associated phenotype was previously reported by Okumura et al. Brain Dev, 2013 PMID: 22633752. HPO-standardized clinical features were: Agenesis of the corpus callosum (HP:0001274); Agyria-pachygyria (HP:0031883, HP:0001302); no Abnormality of the cerebellar vermis (-HP:0002334); Hypoplasia of the brainstem (HP:0002365); Cerebellar hypoplasia (HP:0001321); Hypoplastic hippocampus (HP:0025517); Dilation of lateral ventricles (HP:0006956); Abnormality of the internal capsule (HP:0012502); no Congenital microcephaly (-HP:0011451); Microcephaly (HP:0000252); Generalized tonic-clonic seizures, Infantile spasms (HP:0002069, HP:0012469)

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.