ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.224T>C (p.Ile75Thr) (rs876660839)

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
Ambry Genetics RCV000222796 SCV000278584 uncertain significance Hereditary cancer-predisposing syndrome 2015-09-23 criteria provided, single submitter clinical testing Insufficient or inconclusive evidence
Invitae RCV000547962 SCV000625137 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2017-04-16 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 75 of the MLH1 protein (p.Ile75Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with an MLH1-related disease. ClinVar contains an entry for this variant (Variation ID: 234084). 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. In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Color RCV000222796 SCV000684807 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-18 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.