Submissions for variant NM_006009.4(TUBA1A):c.424G>T (p.Gly142Cys)

dbSNP: rs1555162407

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000497965	SCV000589375	likely pathogenic	not provided	2017-04-10	criteria provided, single submitter	clinical testing	A variant that is likely pathogenic has been identified in the TUBA1A gene. The G142C variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The G142C variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The G142C 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 alters a highly conserved position in the predicted GTP binding domain of the TUBA1A protein. A missense variant in a nearby residue (V137D) has been reported in association with lissencephaly with cerebellar hypoplasia; however, the clinical significance of the V137D change is unknown as parental studies were not performed (Kumar et al, 2010). In silico analysis predicts the G142C variant is probably damaging to the protein structure/function. Additionally, targeted parental testing indicates this variant is apparently de novo. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg	RCV000767511	SCV000898126	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.424G>T, p.(Gly142Cys) variant has been reported as a variant of germline/unknown origin.