"Massively parallel functional testing of MSH2 missense variants conferring Lynch syndrome risk"
Lynch syndrome (MIM: 120435), the first discovered familial cancer syndrome,1 confers predisposition to colorectal and endometrial cancers due to loss of DNA mismatch repair (MMR) and the resulting mutagenic burden.2, 3, 4, 5 Most affected individuals inherit a single loss-of-function variant in one of four MMR factors (MSH2, MLH1, MSH6, PMS2), followed by a somatic “second hit” inactivating the remaining functional copy. Due to high prevalence in the general population (≥1:300),6,7 clear genetic etiology, and potential for prevention through intensified surveillance, pathogenic MMR gene variants are considered clinically actionable.8 Though screening for MMR gene variants is increasingly routine, accurately interpreting them imposes a substantial clinical burden.
Full Article Here: https://www.cell.com/ajhg/fulltext/S0002-9297(20)30439-0
Jia X, Burugula BB, Chen V, Lemons RM, Jayakody S, Maksutova M, Kitzman JO. Massively parallel functional testing of MSH2 missense variants conferring Lynch syndrome risk. Am J Hum Genet. 2020 Dec 17:S0002-9297(20)30439-0. doi:10.1016/j.ajhg.2020.12.003. Epub ahead of print. PMID: 33357406(link is external).