ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.27G>A (p.Arg9=) (rs759680369)

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
Ambry Genetics RCV000166655 SCV000217460 likely benign Hereditary cancer-predisposing syndrome 2014-10-30 criteria provided, single submitter clinical testing
Invitae RCV000471119 SCV000555984 likely pathogenic Hereditary nonpolyposis colon cancer 2018-11-12 criteria provided, single submitter clinical testing This sequence change affects codon 9 of the MLH1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the MLH1 protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals with Lynch syndrome, and shown to segregate in families with Lynch syndrome-associated tumors (PMID: 29790873, 22878509, Invitae). ClinVar contains an entry for this variant (Variation ID: 186982). 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 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.