ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.940del (p.Gln314fs)

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
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV004018121 SCV004848377 likely pathogenic Lynch syndrome 2021-10-27 criteria provided, single submitter clinical testing The p.Gln314ArgfsX17 (c.940del) variant in MSH2 has not been reported in MSH2-associated conditions or in large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 314 and leads to a premature termination codon 17 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the MSH2 gene is an established disease mechanism in autosomal dominant Lynch syndrome. Another variant, c.939del, resulting in the same frameshift at this position, has been identified in a family with Lynch syndrome (Bonadona 2011 PMID: 21642682). In summary, although additional studies are required to fully establish its clinical significance, the p.Gln314ArgfsX17 variant meets criteria to be classified as likely pathogenic for Lynch syndrome. ACMG/AMP criteria applied: PVS1, PM2_Supporting.

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.