ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.307-2A>G (rs267607732)

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
GeneDx RCV000214340 SCV000279729 likely pathogenic not provided 2015-12-29 criteria provided, single submitter clinical testing This variant is denoted MLH1 c.307-2A>G or IVS3-2A>G and consists of an A>G nucleotide substitution at the -2 position of intron 3 of the MLH1 gene. This variant destroys a canonical splice acceptor site and is predicted to cause abnormal gene splicing, leading to either an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product. This variant has not, to our knowledge, been published in the literature. However, a different nucleotide substitution at this position, MLH1 c.307-2A>C, has been observed in an individual with a personal and family history of colon cancer whose tumor demonstrated microsatellite instability and loss of MLH1 protein expression as well as in another individual with a personal or family history suspicious for Lynch syndrome (Bartosova 2003, Goldberg 2015), and is classified as likely pathogenic by the International Society for Gastrointestinal Hereditary Tumours Incorporated (InSiGHT). Based on the currently available information, we consider MLH1 c.307-2A>G to be a likely pathogenic variant.
Ambry Genetics RCV000567906 SCV000669518 pathogenic Hereditary cancer-predisposing syndrome 2017-08-15 criteria provided, single submitter clinical testing Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity;Other data supporting pathogenic classification;Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation

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.