To determine the functional consequences of ACTA2 p.R179 variants in human aortic disease in vivo, the ascending aorta from an 8-year-old child with SMDS due to a de novo ACTA2 c.536G>A variant (p.R179H) was assessed using single cell transcriptomics, along with a 12mm diameter distal ascending aortic tissue sample from a 2-year-old heart donor as a control (Fig. 7A,B). This evidence concerns the gene ACTA2 and benign neoplasm.