Aspartic acid at position 661 (D661) is the most frequently mutated residue in the STAT3 SH2 domain, with 156 cases reported in the COSMIC database (Table 1) and the STAT3D661Y and STAT3D661V variants consistently associated with blood cancers in the gnomAD and COSMIC databases. This evidence concerns the gene STAT3 and hematopoietic and lymphoid system neoplasm.