The most common NOTCH1 mutation in CLL results in a premature stop codon affecting the C-terminal portion of the NOTCH1 receptor, leading to an absence of the proline (P), glutamate (E), serine (S), and threonine (T) (PEST) domain, which regulates protein stability and receptor degradation [16]. The gene discussed is NOTCH1; the disease is B-cell chronic lymphocytic leukemia.