ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.1732-2A>G (rs267607852)

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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) RCV000075335 SCV000106332 likely pathogenic Lynch syndrome 2019-06-21 reviewed by expert panel curation Interrupts canonical donor splice site
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000506870 SCV000601364 likely pathogenic not provided 2017-06-06 criteria provided, single submitter clinical testing
Invitae RCV001386351 SCV001586542 pathogenic Hereditary nonpolyposis colorectal neoplasms 2020-02-19 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 15 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 individual(s) with Lynch syndrome (PMID: 8571956, 24090359). ClinVar contains an entry for this variant (Variation ID: 89861). Experimental studies have shown that changes at this splice site disrupt mRNA splicing (PMID: 24090359). 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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