ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.589-1G>T (rs587779027)

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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) RCV000075779 SCV000106789 likely pathogenic Lynch syndrome 2019-06-21 reviewed by expert panel curation Interrupts canonical donor splice site
Invitae RCV001070764 SCV001236032 pathogenic Hereditary nonpolyposis colon cancer 2019-02-20 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 7 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 Lynch syndrome (LS) or clinical features of LS (PMID: 12658575, 12067992, 15178966). This variant is also known as IVS7-1G>T in the literature. ClinVar contains an entry for this variant (Variation ID: 90290). 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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