ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3173-1_3173del (rs587779256)

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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) RCV000074812 SCV000108021 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon (also interrupts canonical acceptor splice site)
Ambry Genetics RCV000567808 SCV000669999 likely pathogenic Hereditary cancer-predisposing syndrome 2016-07-29 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity
Invitae RCV000822708 SCV000963522 likely pathogenic Hereditary nonpolyposis colon cancer 2018-10-16 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 5 of the MSH6 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 individuals in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 89347). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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