ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1520del (p.Pro507fs) (rs1553366510)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000559986 SCV000625277 pathogenic Hereditary nonpolyposis colon cancer 2019-06-25 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Pro507Leufs*19) 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 a family affected with Lynch syndrome (PMID: 27601186). ClinVar contains an entry for this variant (Variation ID:455503). Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). For these reasons, this variant has been classified as Pathogenic.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000604643 SCV000712560 pathogenic Lynch syndrome 2016-11-09 criteria provided, single submitter clinical testing The p.Pro507fs variant in MSH2 has not been previously reported in individuals w ith Lynch Syndrome and was absent from large population studies, though the abil ity of these studies to accurately detect indels may be limited. This variant is predicted to cause a frameshift, which alters the protein?s amino acid sequence beginning at position 507 and leads to a premature termination codon 19 amino a cids downstream. This alteration is then predicted to lead to a truncated or abs ent protein. Heterozygous loss of function of the MSH2 gene is an established di sease mechanism in Lynch Syndrome. In summary, the available evidence suggests t hat this variant is pathogenic for Lynch Syndrome in an autosomal dominant manne r based upon the predicted impact to the protein.

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