In conclusion, using a whole exome sequencing approach in a large pedigree affected with VTE, we identified an extremely rare variant in the Microtubule-associated serine/threonine-protein kinase-2 (MAST2) gene, that is responsible for inherited thrombophilia through a not yet-fully characterized mechanism that involves modulation of the hemostatic balance of endothelial cells. This evidence concerns the gene MAST2 and thrombophilia.