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While the majority of cases results from common risk variants that confer disease cumulatively, a small proportion of BAV cases has a monogenic etiology where penetrant rare variants (RVs) in single genes are disease causing. We assessed the proportion of monogenic BAV cases in 740 non-syndromic and non-familial BAV patients that should be representative for cardiovascular centers of maximum care. We used next generation sequencing- (NGS-) based single-molecule molecular inversion probes (smMIPs) and analyzed all monogenic BAV genes that have been identified so far (<jats:italic>NOTCH1<\/jats:italic>, <jats:italic>SMAD6<\/jats:italic>, <jats:italic>ROBO4<\/jats:italic>, <jats:italic>GATA4<\/jats:italic>, <jats:italic>GATA6<\/jats:italic>, and <jats:italic>ADAMTS19<\/jats:italic>). In these genes, we identified potential damaging RVs in 2% of our patients, which were not significantly enriched compared to 726 population-based controls. We conclude that the contribution of monogenic BAV forms is only small among non-syndromic and sporadic BAV patients.<\/jats:p>","DOI":"10.1038\/s41431-025-01909-7","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T12:25:12Z","timestamp":1752236712000},"page":"1203-1206","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Implications of monogenic bicuspid aortic valve (BAV) forms among sporadic BAV patients"],"prefix":"10.1038","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4182-7157","authenticated-orcid":false,"given":"Christopher M H","family":"Bruenger","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Oeffner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9962-0741","authenticated-orcid":false,"given":"Laura L","family":"Koebbe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"Zimmer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Verena","family":"Veulemans","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matti","family":"Adam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Bigge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1057-465X","authenticated-orcid":false,"given":"Stefanie","family":"Heilmann-Heimbach","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malte","family":"Kelm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan","family":"Baldus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus M","family":"N\u00f6then","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georg","family":"Nickenig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo","family":"Maj","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baravan","family":"Al-Kassou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9217-6457","authenticated-orcid":false,"given":"Johannes","family":"Schumacher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,7,11]]},"reference":[{"key":"1909_CR1","doi-asserted-by":"publisher","first-page":"2789","DOI":"10.1016\/j.jacc.2009.12.068","volume":"55","author":"SC Siu","year":"2010","unstructured":"Siu SC, Silversides CK. 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