HRAS and Cowden syndrome 1: KRAS (Kirsten RAS) germline mutations are associated with Noonan syndrome (NS; MIM#163950) and cardio-facio-cutaneous syndrome (CFCS; MIM#115150), NRAS (neuroblastoma RAS), RRAS (RAS-related), MRAS (muscle RAS) and RIT1 (RAS-like protein expressed in many tissues 1) also lead to Noonan syndrome, whereas HRAS germline mutations cause Costello syndrome (CS; MIM#218040) (Aoki et al., 2005; Kratz et al., 2006; Schubbert et al., 2006; Cirstea et al., 2010; Flex et al., 2014; Higgins et al., 2017; Niihori et al., 2019).