Submissions for variant NM_000251.3(MSH2):c.1288A>T (p.Lys430Ter)

dbSNP: rs63751646

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)	RCV000076114	SCV000107129	pathogenic	Lynch syndrome	2013-09-05	reviewed by expert panel	research	Coding sequence variation introducing premature termination codon
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001260434	SCV001437431	likely pathogenic	Hereditary nonpolyposis colon cancer	2020-09-16	criteria provided, single submitter	clinical testing	Variant summary: MSH2 c.1288A>T (p.Lys430X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 250314 control chromosomes (gnomAD). c.1288A>T has been reported in the literature at least in an individual affected with Lynch syndrome (Yanus_2020). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. An expert panel (InSiGHT) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.