The identified variants included missense and insertion–deletion (indel) variants within the SH2 (n = 1) and PI3K_P85_iSH2 (n = 16) domains of PIK3R1 and overlapped regions harboring known hotspots seen in cancers (Fig. 1).10–12 Notably, the variants detected in vascular malformation and overgrowth occur in domains that are common to all PIK3R1 products (p85α, p55α, and p50α). Here, PIK3R1 is linked to cancer.