ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.207+1G>A (rs267607718)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000075505 SCV000106501 likely pathogenic Lynch syndrome 2019-06-21 reviewed by expert panel curation Interrupts canonical donor splice site
Ambry Genetics RCV000128866 SCV000172723 pathogenic Hereditary cancer-predisposing syndrome 2019-02-18 criteria provided, single submitter clinical testing Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity;Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
Invitae RCV000627707 SCV000284045 likely pathogenic Hereditary nonpolyposis colon cancer 2019-05-02 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 2 of the MLH1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MLH1-related disease. ClinVar contains an entry for this variant (Variation ID: 90020). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MLH1 are known to be pathogenic (PMID: 15713769, 24362816). 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.
GeneDx RCV000202020 SCV000568563 likely pathogenic not provided 2017-10-16 criteria provided, single submitter clinical testing This variant is denoted MLH1 c.207+1G>A or IVS2+1G>A and consists of a G>A nucleotide substitution at the +1 position of intron 2 of the MLH1 gene. This variant destroys a canonical splice donor 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 been reported in several individuals with personal and/or family histories suggestive of Lynch syndrome (Mangold 2005, Lastella 2011, Laduca 2014, Pearlman 2017). Based on the currently available information, we consider MLH1 c.207+1G>A to be a likely pathogenic variant.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000075505 SCV000592338 pathogenic Lynch syndrome 2012-11-13 criteria provided, single submitter clinical testing
Color RCV000128866 SCV001340138 likely pathogenic Hereditary cancer-predisposing syndrome 2019-11-05 criteria provided, single submitter clinical testing
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000202020 SCV000257084 likely pathogenic not provided no assertion criteria provided research

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.