ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.545+1G>A (rs267607765)

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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) RCV000075748 SCV000106756 likely pathogenic Lynch syndrome 2019-06-21 reviewed by expert panel curation Interrupts canonical donor splice site
Invitae RCV000075748 SCV000543589 pathogenic Lynch syndrome 2016-11-29 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 6 of the MLH1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. Loss-of-function variants in MLH1 are known to be pathogenic. This particular variant has been reported in the literature in individuals affected with Lynch syndrome (PMID: 15849733, 19669161, 20215533, 15879014). Experimental studies have shown that this splice site variant causes exon 6 skipping, leading to a frameshift and premature MLH1 truncation (PMID: 19669161). For these reasons, this variant has been classified as Pathogenic.

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