ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.1687dup (p.Tyr563fs)

dbSNP: rs587779103
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076245 SCV000107264 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation introducing premature termination codon
Ambry Genetics RCV000490897 SCV000580582 pathogenic Hereditary cancer-predisposing syndrome 2018-06-26 criteria provided, single submitter clinical testing The c.1687dupT pathogenic mutation, located in coding exon 11 of the MSH2 gene, results from a duplication of T at nucleotide position 1687, causing a translational frameshift with a predicted alternate stop codon (p.Y563Lfs*5). This mutation has been reported in an individual with a tubular adenoma that had high microsatellite instability (MSI-H) and a loss of MSH2 staining on immunohistochemistry (IHC) (Pino MS et al. J Mol Diagn. 2009 May;11(3):238-47). 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 RCV000689274 SCV000816916 pathogenic Hereditary nonpolyposis colorectal neoplasms 2018-08-01 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). This variant has been reported in an individual affected with Lynch syndrome (PMID: 19324997). This variant is also known as 1687insT in the literature. ClinVar contains an entry for this variant (Variation ID: 90748). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Tyr563Leufs*5) in the MSH2 gene. It is expected to result in an absent or disrupted protein product.
Myriad Genetics, Inc. RCV003452851 SCV004187923 pathogenic Lynch syndrome 1 2023-08-03 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.

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.