ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.1896+1G>A (rs267607867)

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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) RCV000075404 SCV000106400 likely pathogenic Lynch syndrome 2019-06-21 reviewed by expert panel curation Interrupts canonical donor splice site
Invitae RCV000541555 SCV000625105 pathogenic Hereditary nonpolyposis colon cancer 2019-03-01 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 16 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 the literature in individuals affected with Lynch syndrome (PMID: 10422993, 27601186, 12067992). This variant is also known as IVS16+1G>A in the literature. ClinVar contains an entry for this variant (Variation ID: 89925). 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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