NPC1 and Niemann-Pick disease type C: CHK2R145W mutant encoded an unstable protein, which was degraded rapidly by the proteosome pathway.[44] Functional characterization of rare germline missense BRCA1 variants also identified a subset (p.M297V, p.D1152N, p.L52F, p.L1439F, and p.G890R) that exhibited reduced protein stability.[45] Niemann‐Pick type C disease, a fatal neurodegenerative disorder, was caused by loss‐of‐function mutations in the NPC1 gene.