ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3256C>G (p.Pro1086Ala) (rs756108143)

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
Invitae RCV000226723 SCV000283796 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-08-16 criteria provided, single submitter clinical testing This sequence change replaces proline with alanine at codon 1086 of the MSH6 protein (p.Pro1086Ala). The proline residue is weakly conserved and there is a small physicochemical difference between proline and alanine. This variant is present in population databases (rs756108143, ExAC 0.01%). This variant has not been reported in the literature in individuals with MSH6-related disease. ClinVar contains an entry for this variant (Variation ID: 237186). 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 tolerated, 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 RCV000482939 SCV000569278 uncertain significance not provided 2018-01-30 criteria provided, single submitter clinical testing This variant is denoted MSH6 c.3256C>G at the cDNA level, p.Pro1086Ala (P1086A) at the protein level, and results in the change of a Proline to an Alanine (CCC>GCC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MSH6 Pro1086Ala was not observed in large population cohorts (Lek 2016). MSH6 Pro1086Ala is located in the ATPase domain (Warren 2007, Kansikas 2011). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether MSH6 Pro1086Ala is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Counsyl RCV000662522 SCV000785079 uncertain significance Hereditary nonpolyposis colorectal cancer type 5 2017-04-06 criteria provided, single submitter clinical testing
Color RCV000774607 SCV000908413 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-08 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.