Submissions for variant NM_006009.4(TUBA1A):c.17C>G (p.Ser6Cys)

dbSNP: rs1057520574

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000423889	SCV000516100	pathogenic	not provided	2015-04-13	criteria provided, single submitter	clinical testing	The S6C variant in the TUBA1A gene has not been reported previously as a pathogenic variantnor as a benign polymorphism, to our knowledge. The S6C variant was not observed in approximately6500 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 S6C variant is a non-conservativeamino acid substitution, which is likely to impact secondary protein structure as these residues differ inpolarity, charge, size and/or other properties. This substitution occurs at a position that is conserved acrossspecies. In silico analysis predicts this variant is probably damaging to the protein structure/function. Amissense variant in a nearby residue (I5L) has been reported in the Human Gene Mutation Database inassociation with polymicrogyria (Stenson et al., 2014), supporting the functional importance of this region ofthe protein. We interpret S6C as a pathogenic variant.
Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg	RCV000767454	SCV000898069	likely pathogenic	Tubulinopathy	2018-07-01	criteria provided, single submitter	literature only	A variant that is classified as likely pathogenic has been identified in the TUBA1A gene in a born individual of unknown sex. The c.17C>G, p.(Ser6Cys) variant has been reported as a variant of germline/unknown origin.