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

dbSNP: rs63750845

Total submissions: 4

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.
Clinical Genetics Laboratory, Skane University Hospital Lund	RCV001269967	SCV005199178	pathogenic	not provided	2022-12-13	criteria provided, single submitter	clinical testing