ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.925C>T (p.Pro309Ser) (rs267607808)

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 RCV000684787 SCV000259481 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2020-10-01 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 309 of the MLH1 protein (p.Pro309Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. This variant is present in population databases (rs267607808, ExAC 0.006%). This variant has been observed in an individual affected with colon cancer (PMID: 18033691). ClinVar contains an entry for this variant (Variation ID: 90444). 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 RCV000486267 SCV000567201 uncertain significance not provided 2020-12-24 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 18033691, 25871441)
Ambry Genetics RCV000574268 SCV000662018 likely benign Hereditary cancer-predisposing syndrome 2019-01-30 criteria provided, single submitter clinical testing Subpopulation frequency in support of benign classification
Color Health, Inc RCV000574268 SCV000689930 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-02 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.