ClinVar Miner

Submissions for variant NM_000553.5(WRN):c.3454A>G (p.Thr1152Ala) (rs1309001891)

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
Invitae RCV000633259 SCV000754476 uncertain significance Werner syndrome 2017-08-09 criteria provided, single submitter clinical testing This sequence change replaces threonine with alanine at codon 1152 of the WRN protein (p.Thr1152Ala). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and alanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with WRN-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. In addition, an experimental study has shown that the Thr1152Ala missense change, in combination with additional WRN missense changes, results in reduced ATR phosphorylation at residues important for correct WRN nuclear localization and replication protein A (RPA) co-localization (PMID: 20802463). However, the clinical significance of this finding is unclear, as the impact of each individual missense change was not specifically assessed. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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.