The NM_000251.3(MSH2):c.929T>G (p.Leu310Arg) variant is a missense variant replacing Leucin 310 to Arginin. The variant has been reported to co-segregate with disease in pedigree(s) with a combined* Bayes Likelihood Ratio >18.72 in ≥2 families (PMID: 30376427, 33848333) (PP1_STR). The variant is a missense variant with MAPP+PolyPhen-2 prior probability for pathogenicity >0.81 as per http://priors.hci.utah.edu/PRIORS (PP3_MOD). The variant is a missense change at an amino acid residue where a different missense change was classified by this VCEP as Pathogenic on the protein level; p.Leu310Pro classified as Class 5 by InSiGHT (PM5). The variant has been detected in at least 2 independent CRC/Endometrial MSI-H tumours using a standard panel of 5-10 markersg and/or loss of MMR protein expression consistent with the variant location (PP4_MOD). The variant is not reported in gnomAD v4.1 (PM2_SUP). In summary, this variant meets the criteria to be classified as pathogenic for autosomal-dominant inherited Lynch-syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis: criteria PM5, PP1_strong, PP4_moderate, PP3_moderate and PM2_supporting applied. (VCEP specifications version 1)