Submissions for variant NM_000251.3(MSH2):c.1442_1445dup (p.Arg482fs)

dbSNP: rs63750930

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001175539	SCV001339160	likely pathogenic	Hereditary nonpolyposis colon cancer	2020-03-09	criteria provided, single submitter	clinical testing	Variant summary: MSH2 c.1442_1445dupTAAG (p.Arg482SerfsX7) 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. The variant was absent in 251308 control chromosomes (gnomAD). To our knowledge, no occurrence of c.1442_1445dupTAAG in individuals affected with Lynch Syndrome has been reported. At least one publication reports experimental evidence evaluating an impact on protein function, demonstrating nearly absent mismatch repair activity in an endometrial adenocarcinoma derived cell line carrying the variant of interest together with a nonsense variant in trans (Boyer_1995). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.