Definite loss-of-function mutations in the TSC1 and/or TSC2 genes with dysregulation of the mTOR pathway (which is sufficient but not necessary for the diagnosis of TSC). TSC1 and/or TSC2 mutations that are unclear or of no functional significance do not meet these criteria, and therefore, they cannot be used in the diagnosis of TSC. The gene discussed is TSC1; the disease is tuberous sclerosis.