ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.1731+1G>T (rs267607853)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000075324 SCV000106318 likely pathogenic Lynch syndrome 2019-06-21 reviewed by expert panel curation Interrupts canonical donor splice site
Counsyl RCV000576509 SCV000677751 likely pathogenic Lynch syndrome II 2017-04-17 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000075324 SCV000696120 likely pathogenic Lynch syndrome 2017-02-07 criteria provided, single submitter clinical testing Variant summary: The MLH1 c.1731+1G>T variant involves the alteration of a conserved intronic nucleotide. Mutation Taster predicts a damaging outcome for this variant. 4/5 splice prediction tools predict a significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant is absent in 121174 control chromosomes. In addition, one reputable database classified this variant as likely pathogenic. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and clinical diagnostic laboratories. Taken together, this variant is classified as likely pathogenic.
Invitae RCV000685725 SCV000813217 likely pathogenic Hereditary nonpolyposis colorectal neoplasms 2020-09-02 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 15 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). Disruption of this splice site has been observed in individuals affected with colon cancer (PMID: 28449805, 8571956, 15365995, 16034045). This variant has been reported in an individual in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 89850). 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 RCV001567027 SCV001790640 likely pathogenic not provided 2019-08-01 criteria provided, single submitter clinical testing Canonical splice site variant in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 30068706, 24362816, 21520333, 28449805, 15713769)

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.