PIK3CA and thyroid gland disorder: Although the heterozygous GC genotype, and most likely also the homozygous CC genotype, are demonstrated to predispose to development of NMTC by inducing hyperactivation of the PI3K-Akt-mTOR pathway upon the encounter of activating stimuli, it should be emphasized that this germline genetic variant is not capable of evoking thyroid tumorigenesis by itself because of limited genetic penetrance, but rather represents a risk modifier.