ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.1213_1217dup (p.Leu407fs)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV004018090 SCV004847754 likely pathogenic Lynch syndrome 2019-05-08 criteria provided, single submitter clinical testing The p.Leu407ThrfsX7 variant in MSH2 has not been previously reported in individuals with Lynch syndrome and was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 407 and leads to a premature termination codon 7 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the MSH2 gene is an established disease mechanism in autosomal dominant Lynch syndrome. In summary, although additional studies are required to fully establish its clinical significance, the p.Leu407ThrfsX7 variant meets criteria to be classified as likely pathogenic for Lynch syndrome. ACMG/AMP criteria applied: PVS1, PM2.

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