RET and Hirschsprung disease: In contrast, RET mutations found in HSCR patients are all LOF mutations (Carlomagno et al., 1996) and can be roughly divided into two groups: 1) null variants with the production of a truncated protein due to a nonsense mutation, frameshift insertion/deletion or canonical ±1 or 2 splice site mutation; and 2) variant of uncertain significance, such as a missense mutation, in-frame insertion/deletion, or noncanonical splice site mutation.