PLK4 and RASopathy: Well-defined functional domains (PM1) were assessed for the 7 new RASopathy-associated genes: MRAS, NRAS, RIT1, RRAS2, SOS2, LZTR1, and PPP1CB. The RAS gene family has 4 functional domains that qualify for PM1: the P-Loop, switch 1 region (SW1), switch 2 region (SW2), and SAK motif.31, 32, 33, 34 All RAS family members contain the first 3 domains; however, MRAS, RIT1, and RRAS2 lack the SAK domain (Supplemental Figure 2).