ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.860dup (p.Gln288fs) (rs193922375)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000030255 SCV000052922 likely pathogenic Lynch syndrome 2011-08-18 criteria provided, single submitter curation Converted during submission to Likely pathogenic.
Ambry Genetics RCV000162420 SCV000212761 pathogenic Hereditary cancer-predisposing syndrome 2017-07-21 criteria provided, single submitter clinical testing The c.860dupG pathogenic mutation, located in coding exon 5 of the MSH2 gene, results from a duplication of G at nucleotide position 860, causing a translational frameshift with a predicted alternate stop codon (p.Q288Tfs*3). This pathogenic mutation has been reported in multiple individuals with a personal and/or family history of cancers associated with Lynch syndrome (Guindalini RS et al. Gastroenterology. 2015 Nov;149:1446-53; Espenschied CR et al. J. Clin. Oncol. 2017 Aug;35(22):2568-2575). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Invitae RCV001034633 SCV000284191 pathogenic Hereditary nonpolyposis colorectal neoplasms 2020-07-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln288Thrfs*3) in the MSH2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with Lynch syndrome (PMID: 26248088). ClinVar contains an entry for this variant (Variation ID: 36579). Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). For these reasons, this variant has been classified as 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.