A two base-pair frameshift-deletion (c.7544_7545fsdelCT) accounts for more than 90% of all NOTCH1mut in CLL and results in a stable activated form of NOTCH1 due to the truncation of the C-terminal PEST domain, which is involved in NOTCH1 protein turnover and degradation [4]. The gene discussed is NOTCH1; the disease is B-cell chronic lymphocytic leukemia.