Submissions for variant NM_006009.4(TUBA1A):c.1025A>C (p.Gln342Pro)

dbSNP: rs1555162307

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000521383	SCV000616908	likely pathogenic	not provided	2017-06-08	criteria provided, single submitter	clinical testing	The de novo Q342P variant in the TUBA1A gene has not been published as pathogenic, nor has it been reported as a benign polymorphism to our knowledge. The Q342P variant was not observed in approximately 6,500 individuals of European and African American ancestry in an external variant databasea, indicating it is not a common benign variant in these populations. The Q342P 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 well-conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. A missense variant in a nearby residue (A333V) has been reported in the Human Gene Mutation Database in association with polymicrogyria-like disease (Stenson et al., 2014), supporting the functional importance of this region of the protein. The Q342P variant is a strong candidate for a pathogenic variant. However, the possibility that it may be a rare benign variant cannot be excluded.
Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg	RCV000767457	SCV000898072	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.1025A>C, p.(Gln342Pro) variant has been reported as a variant of germline/unknown origin.