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The aim of this study was to assess genotype\u2010 phenotype correlations, focusing on the cardiac features and outcomes of interventions for cardiac conditions, in a single\u2010center cohort of 116 patients with molecularly confirmed diagnosis of RASopathy, and compare these findings with previously published data. All enrolled patients underwent a comprehensive echocardiographic examination. Relevant information was also retrospectively collected through the analysis of clinical records. As expected, significant associations were found between <jats:italic>PTPN11<\/jats:italic> mutations and pulmonary stenosis (both valvular and supravalvular) and pulmonary valve dysplasia, and between <jats:italic>SOS1<\/jats:italic> mutations and valvular defects. Similarly, <jats:italic>HRAS<\/jats:italic> mutations were significantly associated with HCM. Potential associations between less prevalent mutations and cardiac defects were also observed, including <jats:italic>RIT1<\/jats:italic> mutations and HCM, <jats:italic>SOS2<\/jats:italic> mutations and septal defects, and <jats:italic>SHOC2<\/jats:italic> mutations and septal and valve abnormalities. Patients with <jats:italic>PTPN11<\/jats:italic> mutations were the most likely to require both a primary treatment (transcatheter or surgical) and surgical reintervention. Other cardiac anomalies less reported until recently in this population, such as isolated functional and structural mitral valve diseases, as well as a sigmoid\u2010shaped interventricular septum in the absence of HCM, were also reported. In conclusion, our study confirms previous data but also provides new insights on cardiac involvement in RASopathies. Further research concerning genotype\/phenotype associations in RASopathies could lead to a more rational approach to surgery and the consideration of drug therapy in patients at higher risk due to age, severity, anatomy, and comorbidities.<\/jats:p>","DOI":"10.1002\/ajmg.a.62529","type":"journal-article","created":{"date-parts":[[2021,10,17]],"date-time":"2021-10-17T00:21:26Z","timestamp":1634430086000},"page":"431-445","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Genotype\u2010cardiac phenotype correlations in a large single\u2010center cohort of patients affected by RASopathies: Clinical implications and literature review"],"prefix":"10.1002","volume":"188","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4089-637X","authenticated-orcid":false,"given":"Chiara","family":"Leoni","sequence":"first","affiliation":[{"name":"Center for Rare Diseases and Birth Defects, Department of Woman and Child Health and Public Health Fondazione Policlinico Universitario A. 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