Phosphorylation at PLCG1-Y783 causes a conformational change that relieves the auto-inhibition of the C-terminal SH2 domain, and leads to downstream signaling.82, 83 Activated PLCG1 catalyzes the conversion of phosphatidylinositol 4,5-bisphosphate to diacylglycerol and inositol 1,4,5-triphosphate, leading to protein kinase C-dependent MAPK signaling.84, 85 A recurring mutation in PLCG1, R707Q, has been identified in angiosarcoma, with a prevalence of 9–30% (refs 12, 13). The gene discussed is PLCG1; the disease is angiosarcoma.