MAP2K1 and Global developmental delay: One example where limited destabilisation can lead to gain-of-function was that of a novel heterozygous missense variant, MAP2K1 NM_002755.4:c.149 T > C p.(Leu50Pro), which was identified as a de novo variant in an infant presenting with facial dysmorphism (including hypertelorism, down slanted palpebral fissures, prominent forehead and small chin), skin abnormalities, joint hypermobility, macrocephaly and global developmental delay.