ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1477C>T (p.Gln493Ter) (rs63750936)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076173 SCV000107189 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation introducing premature termination codon
Ambry Genetics RCV000129104 SCV000183815 pathogenic Hereditary cancer-predisposing syndrome 2017-05-08 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Integrated Genetics/Laboratory Corporation of America RCV000076173 SCV000696216 pathogenic Lynch syndrome 2017-03-30 criteria provided, single submitter clinical testing Variant summary: The MSH2 c.1477C>T (p.Gln493X) variant results in a premature termination codon, predicted to cause a truncated or absent MSH2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.1576delA, p.Thr526fsX17; c.1705_1706delGA, p.Glu569fsX2; c.1777C>T, p.Gln593X). One in silico tool predicts a damaging outcome for this variant. This variant is absent in 121236 control chromosomes and has been reported in multiple affected individuals in the literature. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000630148 SCV000751104 pathogenic Hereditary nonpolyposis colon cancer 2018-12-12 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln493*) 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 several individuals affected with Lynch syndrome (PMID: 27978560, 11975096, 15849733, 28514183, 16216036, 20459533). ClinVar contains an entry for this variant (Variation ID: 90677). Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759818 SCV000889413 pathogenic not provided 2017-12-26 criteria provided, single submitter clinical testing
Color RCV000129104 SCV000905228 pathogenic Hereditary cancer-predisposing syndrome 2017-12-07 criteria provided, single submitter clinical testing

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