Submissions for variant NM_006009.4(TUBA1A):c.1148C>A (p.Ala383Asp)

dbSNP: rs587784482

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000488967	SCV000577845	likely pathogenic	not provided	2017-09-22	criteria provided, single submitter	clinical testing	The A383D variant has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. It 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. The A383D 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 conserved position and missense variants in nearby residues have been reported in the Human Gene Mutation Database in association with TUBA1A-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, GeneDx interprets A383D as a variant, likely pathogenic
Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg	RCV000767440	SCV000898055	pathogenic	Tubulinopathy	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 born individual of unknown sex. The c.1148C>A, p.(Ala383Asp) variant has been reported as a variant of germline/unknown origin.