ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.790+2T>C (rs267607790)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000075851 SCV000106866 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Variant causes splicing aberration interrupting protein function: full inactivation of variant allele.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000075851 SCV000592373 pathogenic Lynch syndrome 2013-03-06 criteria provided, single submitter clinical testing
Invitae RCV000812444 SCV000952757 pathogenic Hereditary nonpolyposis colon cancer 2018-12-07 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 9 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 several families affected with Lynch syndrome (PMID: 12624141, 15713769), and has also been observed in several individuals affected with Lynch syndrome-related cancers (PMID: 19698169, 22883484, 25081409). This variant is also known as IVS9+2T>C in the literature. ClinVar contains an entry for this variant (Variation ID: 90360). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 15713769). 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.

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