ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.306+1G>A (rs267607734)

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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) RCV000075628 SCV000106630 pathogenic Lynch syndrome I 2015-11-24 reviewed by expert panel research
Invitae RCV000544543 SCV000625143 pathogenic Hereditary nonpolyposis colon cancer 2017-07-27 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 3 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 reported in several individuals affected with Lynch syndrome (PMID: 10471527, 11151427, 15849733, 27601186). ClinVar contains an entry for this variant (Variation ID: 90142). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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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