ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1021C>G (p.Leu341Val) (rs748115066)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000220354 SCV000276256 uncertain significance Hereditary cancer-predisposing syndrome 2014-07-17 criteria provided, single submitter clinical testing Insufficient or Conflicting Evidence
Invitae RCV000232111 SCV000284087 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-11-04 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 341 of the MSH2 protein (p.Leu341Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. This variant is present in population databases (rs748115066, ExAC 0.001%). This variant has been observed in an individual with suspected Lynch syndrome (PMID: 23354017), in healthy individuals (PMID: 26344056), as well as an individual with colon polyps in the Universal Mutation Database (PMID: 22144684). ClinVar contains an entry for this variant (Variation ID: 232192). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
GeneDx RCV000236110 SCV000293975 uncertain significance not provided 2018-06-14 criteria provided, single submitter clinical testing This variant is denoted MSH2 c.1021C>G at the cDNA level, p.Leu341Val (L341V) at the protein level, and results in the change of a Leucine to a Valine (CTT>GTT). This variant has been observed in one individual with colorectal cancer whose tumor demonstrated loss of MSH2 and MSH6 proteins via immunohistochemistry (IHC) as well as in one individual with uterine cancer (Rodr?guez-Soler 2013, Yehia 2018). MSH2 Leu341Val was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the Lever domain (L?tzen 2008, Kansikas 2011). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether MSH2 Leu341Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Counsyl RCV000662429 SCV000784883 uncertain significance Lynch syndrome I 2017-01-17 criteria provided, single submitter clinical testing
Color RCV000220354 SCV000908289 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-17 criteria provided, single submitter clinical testing

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.