ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.873_876del (p.Thr292fs) (rs587779191)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076741 SCV000107778 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
Ambry Genetics RCV000575858 SCV000673904 pathogenic Hereditary cancer-predisposing syndrome 2017-06-21 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Invitae RCV000629801 SCV000750757 pathogenic Hereditary nonpolyposis colon cancer 2017-12-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Thr292Leufs*8) in the MSH2 gene. It is expected to result 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 affected with Lynch syndrome (PMID: 15217520, 15849733). ClinVar contains an entry for this variant (Variation ID: 91236). Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000657243 SCV000778972 pathogenic not provided 2017-10-30 criteria provided, single submitter clinical testing This deletion of four nucleotides in MSH2 is denoted c.873_876delGACT at the cDNA level and p.Thr292LeufsX8 (T292LfsX8) at the protein level. The normal sequence, with the bases that are deleted in brackets, is AACT[delGACT]ACTT. The deletion causes a frameshift which changes a Threonine to a Leucine at codon 292, and creates a premature stop codon at position 8 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. MSH2 c.873_876delGACT has been reported in multiple individuals with Lynch syndrome (Kunstmann 2004, Mangold 2005, Bonadona 2011). We consider this variant to be pathogenic.

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