Figure 1.

Multi-tissue workup of TP53 pathogenic variants (PV) identified in germline (blood/saliva) commercial testing. This diagram depicts a diagnostic flowchart for establishing the presence/absence and variant allele fraction (VAF) of TP53 PVs in multiple tissues, often representing different embryonic germ layers, to discern and subclassify germline status including parental gonadal mosaicism, “de novo” germline status, post-zygotic mosaicism (PZM), or clonal hematopoiesis (CH) as ACE in a single tissue compartment. CH is further differentiated into clonal hematopoiesis of indeterminant potential (CHIP) if the complete blood count (CBC) is normal or extant hematologic neoplasia if not, and the approach for prospective evaluation of clonal evolution and genomic drivers of CH, and clinical state change is outlined.