This lecture discusses the consequences of mutations, ranging from devastating monoallelic diseases like Huntington's disease to common variants such as APOE4 increasing the risk of Alzheimer's. It explains how genetic variability is crucial in medicine, leading to novel insights, clinical advances, and improved personalized medicine. The lecture also covers the various consequences of mutations at the gene expression and epigenetic levels, emphasizing the importance of understanding cis and trans effects in gene regulatory networks.