Although it was previously hypothesized that patients with LOF mutations in TGFB3 lack cardiovascular phenotypes (16), we clearly demonstrate that TGFB3 LOF mutations associate with aortic and other arterial aneurysms/dissections and mitral valve disease, and recognize an extremely variable cardiovascular phenotype in the TGFB3 cohort described here. Here, TGFB3 is linked to mitral valve disorder.