ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.1587del (p.Glu530fs)

dbSNP: rs63750845
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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) RCV000076201 SCV000107218 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation introducing premature termination codon
Clinical Genetics and Genomics, Karolinska University Hospital RCV001269967 SCV001450361 pathogenic not provided 2017-06-26 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000076201 SCV004848350 likely pathogenic Lynch syndrome 2020-05-13 criteria provided, single submitter clinical testing The p.Glu530LysfsX13 variant in MSH2 has been reported in one individual with microsatellite unstable colon cancer who had a family history of colon cancer (Nilbert 1999). It was absent from large population studies. This variant was classified as pathogenic on 09/05/2013 by the ClinGen-approved International Society for Gastrointestinal Hereditary Tumours (InSiGHT) expert panel (Variation ID 90704). This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 530 and leads to a premature termination codon 13 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, this variant meets criteria to be classified as likely pathogenic for autosomal dominant Lynch syndrome. ACMG/AMP Criteria applied: PVS1, PM2.

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