NOTCH1 and neoplasm: The CLL driver gene mutations with VAFs <1% (IRF4, NOTCH1, SF3B1 and TP53; in pts-6, 8, 9, 13) at TP1 were ascertained by manual curation of the TDR sequencing reads (Supplementary Table S6) after being originally detected in later tumour TPs with a higher VAF, suggesting a larger sub-clonal population at progression.