ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.206G>A (p.Arg69Lys) (rs63751661)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000580736 SCV000684794 uncertain significance Hereditary cancer-predisposing syndrome 2018-12-27 criteria provided, single submitter clinical testing
Invitae RCV000692100 SCV000819908 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-11-27 criteria provided, single submitter clinical testing This sequence change replaces arginine with lysine at codon 69 of the MLH1 protein (p.Arg69Lys). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333. ClinVar contains an entry for this variant (Variation ID: 489896). This variant has been reported to have conflicting or insufficient data to determine the effect on MLH1 protein function (PMID: 17510385, 11555625). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, but this prediction has not been confirmed by published transcriptional studies. 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.

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.