ClinVar Miner

Submissions for variant NM_000489.5(ATRX):c.517G>A (p.Ala173Thr) (rs1064795090)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000483710 SCV000570552 pathogenic not provided 2018-10-29 criteria provided, single submitter clinical testing The A173T variant in the ATRX gene has not been published as a pathogenic variant, nor as a benign variant, to our knowledge. This variant was observed as hemizygous in two male probands tested at GeneDx who had features consistent with an ATRX-related disorder. The A173T variant was found to be apparently de novo in one of these probands, and apparently de novo in the mother of the other proband. This variant is not observed in large population cohorts (Lek et al., 2016). The A173T 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 within the DNA-binding ATRX-DNMT3-DNMT3L (ADD) domain of the ATRX protein, and missense variants in nearby residues (G175E and V178D) have been reported in the Human Gene Mutation Database in association with ATRX-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. We interpret A173T as a pathogenic variant.

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.