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 2017-04-04 criteria provided, single submitter clinical testing This sequence change deletes 1 nucleotide from exon 10 of the MSH2 mRNA (c.1520delC), causing a frameshift at codon 507. This creates a premature translational stop signal (p.Pro507Leufs*19) and is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH2 are known to be pathogenic. This particular variant has been reported in a family affected with Lynch syndrome (PMID: 27601186). 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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