ClinVar Miner

Submissions for variant NM_000553.6(WRN):c.111G>C (p.Lys37Asn)

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
Labcorp Genetics (formerly Invitae), Labcorp RCV003011812 SCV003306007 likely pathogenic Werner syndrome 2023-07-06 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with WRN-related conditions. This variant is present in population databases (rs771433734, gnomAD 0.0009%). This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 37 of the WRN protein (p.Lys37Asn). RNA analysis indicates that this missense change induces altered splicing and may result in an absent or disrupted protein product. ClinVar contains an entry for this variant (Variation ID: 2088780). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Studies have shown that this missense change results in activation of a cryptic splice site and introduces a premature termination codon (Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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.