ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1276+1G>A (rs267607950)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000491508 SCV000580472 pathogenic Hereditary cancer-predisposing syndrome 2015-11-12 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Functionally-validated splicing mutation
Color RCV000491508 SCV000684922 likely pathogenic Hereditary cancer-predisposing syndrome 2018-09-04 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000076086 SCV000592495 pathogenic Lynch syndrome 2014-05-07 criteria provided, single submitter clinical testing
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076086 SCV000107101 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Multifactorial likelihood analysis posterior probability >0.99
Invitae RCV000548164 SCV000625246 pathogenic Hereditary nonpolyposis colon cancer 2018-11-12 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 7 of the MSH2 gene. It is expected to disrupt RNA splicing and likely results in a disrupted protein product. This variant is not present in population databases (rs267607950, ExAC no frequency). This variant has been reported in individuals affected with Lynch syndrome (PMID: 15849733, 19669161, 21520333). ClinVar contains an entry for this variant (Variation ID: 90590). Experimental studies have shown that this splice donor change causes the activation of a cryptic splice site in exon 7 resulting in the in-frame deletion of 16 amino acids in vitro (PMID: 19669161). Deletion of this region is expected to disrupt the MSH3/MSH6 interaction domain, which is required for proper MSH2 protein function (PMID: 18822302, 9774676). For these reasons, this variant has been classified as Pathogenic.
MutSpliceDB: a database of splice sites variants effects on splicing,NIH RCV000786795 SCV000925685 not provided not provided no assertion provided in vitro

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