ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.425C>G (p.Ser142Ter) (rs63750910)

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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) RCV000076598 SCV000107633 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
GeneDx RCV000519167 SCV000617591 pathogenic not provided 2017-08-21 criteria provided, single submitter clinical testing This variant is denoted MSH2 c.425C>G at the cDNA level and p.Ser142Ter (S142X) at the proteinlevel. The substitution creates a nonsense variant, which changes a Serine to a premature stop codon (TCA>TGA),and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNAdecay. This variant has been reported in association with Lynch syndrome (Hampel 2005, Haroldsdottir 2016, Sunga2017) and is considered pathogenic
Ambry Genetics RCV001022162 SCV001183863 pathogenic Hereditary cancer-predisposing syndrome 2019-01-29 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Invitae RCV001071576 SCV001236886 pathogenic Hereditary nonpolyposis colorectal neoplasms 2019-01-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser142*) 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 observed in individuals affected with Lynch syndrome (PMID: 14514376, 28449805, 28874130, 15872200). ClinVar contains an entry for this variant (Variation ID: 91096). Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). For these reasons, this variant has been classified as Pathogenic.

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