Interestingly, the Ras-activating PTPN11 (SHP2) p.Tyr63Cys variant identified in KVOGM23-1 was previously identified in Noonan syndrome (OMIM# 163950), which features a broad spectrum of congenital heart defects and other systemic vascular lesions78,79. Here, PTPN11 is linked to Noonan syndrome.