ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.340G>T (p.Glu114Ter) (rs878853815)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000228392 SCV000919697 likely pathogenic Lynch syndrome 2018-03-30 criteria provided, single submitter clinical testing Variant summary: MSH2 c.340G>T (p.Glu114X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the 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 (eg. c.387_388delTC, p.Gln130fsX2; c.528_529delTG, p.Cys176X; c.704_705delAA, p.Lys235fsX20). The variant was absent in 121212 control chromosomes (ExAC). To our knowledge, no occurrence of c.340G>T in individuals affected with Lynch Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submission for a clinical diagnostic laboratory (evaluation after 2014) and a reputable database cite the variant as "pathogenic." Based on the evidence outlined above, the variant was classified as likely pathogenic.
Invitae RCV000228392 SCV000284166 pathogenic Lynch syndrome 2016-02-14 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 114 (p.Glu114*) of the MSH2 gene. It is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, truncating variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). For these reasons, this variant has been classified as Pathogenic.

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