ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.1989+1G>A (rs267607879)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000075455 SCV000106452 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Multifactorial likelihood analysis posterior probability >0.99
Invitae RCV000691557 SCV000819343 likely pathogenic Hereditary nonpolyposis colon cancer 2018-06-08 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 17 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 individuals affected with colorectal cancer (PMID: 14635101, 15289847, 15849733, 20233461). This variant is also known as IVS17+1G>A in the literature. ClinVar contains an entry for this variant (Variation ID: 89973). 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.

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