ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.1667+2_1667+8delinsATTT

dbSNP: rs587778938
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000075298 SCV000106291 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Variant causes splicing aberration, >2 MSI-H, segregation with disease & <0.01% in controls
Labcorp Genetics (formerly Invitae), Labcorp RCV001201384 SCV000543624 pathogenic Hereditary nonpolyposis colorectal neoplasms 2020-02-20 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 14 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 been observed in individual(s) with Lynch syndrome (PMID: 22864660, 23329266, 9245993, 18566915). ClinVar contains an entry for this variant (Variation ID: 89824). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 9245993). 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). For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc. RCV003451047 SCV004185940 pathogenic Colorectal cancer, hereditary nonpolyposis, type 2 2023-07-21 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function. mRNA analysis has demonstrated abnormal mRNA splicing occurs [PMID: 15300854].
All of Us Research Program, National Institutes of Health RCV000075298 SCV004825837 pathogenic Lynch syndrome 2023-08-16 criteria provided, single submitter clinical testing This variant disrupts a canonical splice site and is predicted to result in abnormal splicing. Aberrant splicing and/or loss of function is an established mechanism of disease. This prediction has been confirmed by an RNA splicing assay (PMID: 9245993). This variant has been reported in multiple individuals with Lynch syndrome (PMID: 22864660, 23329266, 9245993, 18566915). This variant is absent from or rare in large population databases, including the Genome Aggregation Database (http://gnomad.broadinstitute.org/).
Clinical Genetics Laboratory, Skane University Hospital Lund RCV004696682 SCV005197419 pathogenic not provided 2024-02-15 criteria provided, single submitter clinical testing
GeneReviews RCV001804814 SCV002054054 not provided Lynch syndrome 1 no assertion provided literature only

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.