ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1373T>G (p.Leu458Ter) (rs63750521)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076136 SCV000107151 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation introducing premature termination codon
GeneDx RCV000160582 SCV000211175 pathogenic not provided 2014-06-11 criteria provided, single submitter clinical testing This pathogenic variant is denoted MSH2 c.1373T>G at the cDNA level and p.Leu458Ter (L458X) at the protein level. The substitution creates a nonsense variant, which changes a Leucine to a premature stop codon (TTA>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in multiple families with early-onset colon, endometrial and ovarian cancers, consistent with Lynch syndrome (Liu 1994, Ichikawa 1999, Mangold 2005, Wahlberg 2005). MSH2 Leu458Stop was also observed in a proband with colon cancer and several sebaceous neoplasms whose family history included colon and breast cancers, consistent with the Muir Torre variant of Lynch syndrome (Mangold 2004). This variant is considered pathogenic.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000076136 SCV000592499 pathogenic Lynch syndrome 2014-03-27 criteria provided, single submitter clinical testing

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