ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.292G>A (p.Gly98Ser) (rs267607725)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000524286 SCV000543593 likely pathogenic Hereditary nonpolyposis colorectal neoplasms 2017-10-30 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 98 of the MLH1 protein (p.Gly98Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with suspected Lynch syndrome (PMID: 22290698, 185612205). It has also been shown to segregate with Lynch syndrome-associated cancers in several families (Invitae). ClinVar contains an entry for this variant (Variation ID: 90128). An algorithm developed specifically for the MLH1 gene suggests that this missense change is likely to be deleterious (PMID: 22290698). However, this prediction has not been confirmed by published functional studies and its clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, 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.