ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3632T>C (p.Leu1211Pro) (rs864622041)

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
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000206750 SCV000259176 pathogenic Lynch syndrome 2019-06-21 reviewed by expert panel curation Multifactorial likelihood analysis posterior probability >0.99
Ambry Genetics RCV000215362 SCV000273358 likely pathogenic Hereditary cancer-predisposing syndrome 2019-06-05 criteria provided, single submitter clinical testing Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation;In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Structural Evidence;Rarity in general population databases (dbsnp, esp, 1000 genomes)
Invitae RCV000471873 SCV000551224 likely pathogenic Hereditary nonpolyposis colon cancer 2019-12-17 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 1211 of the MSH6 protein (p.Leu1211Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed in families affected with Lynch syndrome-associated tumors (PMID: 28874130, Invitae). This variant has also been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 219294). 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 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.