NGS on both peripheral blood and lesional tissue was performed on patient 20, presenting with angiodysplastic lesions on visceral sites, cavernous hemangiomas, and intestinal polyposis unmasked both a germline heterozygous VUS on SMAD4 c.1301A > C (p.(Tyr434Ser)), inherited from the healthy mother and a somatic pathogenic variant on COL3A1 c.4096C > T (p.(Gln1366*)) with a VAF of 2%. This evidence concerns the gene SMAD4 and cavernous hemangioma.