FBN1 and Marfan syndrome: In the early 1990s, pathogenic variants in FBN1 were identified as the cause of MFS.1,13 Pathogenic variants predisposing to MFS are distributed throughout the gene and are mostly private.8 Missense variants typically disrupting the repetitive calcium-binding epidermal growth factor (cb-EGF)–like domains are the most common type of disease-causing variants.14 Approximately 10% of the disease-causing variants disrupt canonical splice donor or acceptor sites and cause splicing errors, which can lead to in-frame deletion of an entire cb-EGF–like domain.