We next examined the MAPK/ERK pathway using three variants of RAF1 against which the RAF1T543M can be evaluated: RAF1WT, a gain‐of‐function (GoF) allele RAF1S257L (positive control), the most common activating mutation associated with HCM in Noonan syndrome, and the heterozygous‐acting loss‐of‐function (LoF) RAF1L603P mutation associated with childhood‐onset dilated cardiomyopathy (negative control) (Dhandapany et al, 2014; Jaffré et al, 2019). This evidence concerns the gene MAPK1 and Noonan syndrome.