F2 and Venous thrombosis: Prothrombin G20210A are correlated with ~ 2-4-fold risk for thrombosis in heterozygotes [8], while variants in prothrombin Arg596 residue (e.g. Arg596Leu, Arg596Gln) were correlated with high thrombotic risk and identified as significant pathogenic variants according to American College of Medical Genetics guidelines [9–11].