ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.794G>C (p.Arg265Pro) (rs63751448)

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) RCV000680199 SCV000807663 likely pathogenic Lynch syndrome I 2018-06-13 reviewed by expert panel curation Multifactorial likelihood analysis posterior probability > 0.95 (0.969)
Ambry Genetics RCV000567811 SCV000673828 likely pathogenic Hereditary cancer-predisposing syndrome 2019-10-10 criteria provided, single submitter clinical testing Other strong data supporting pathogenic classification;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;Rarity in general population databases (dbsnp, esp, 1000 genomes)
Invitae RCV001212266 SCV001383846 likely pathogenic Hereditary nonpolyposis colorectal neoplasms 2019-08-13 criteria provided, single submitter clinical testing This sequence change replaces arginine with proline at codon 265 of the MLH1 protein (p.Arg265Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with clinical features of Lynch syndrome (PMID: 28874130, 24344984), and observed to segregate with Lynch syndrome in a family (PMID: 19423266). ClinVar contains an entry for this variant (Variation ID: 433856). Based on a multifactorial likelihood algorithm using genetic data, this variant has been determined to have a high probability of being pathogenic (PMID: 24362816). This variant has been reported to affect MLH1 protein function (PMID: 29520894). 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.