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Diagnosis is confirmed by detecting heterozygous variants in <jats:italic>COL3A1<\/jats:italic>. This is the largest Asian case series and the first to apply an amplification\u2010based next\u2010generation sequencing through custom panels of causative genes for HCTDs, including a specific method of evaluating copy number variations. Among 429 patients with suspected HCTDs analyzed, 101 were suspected to have vEDS, and 33 of them (32.4%) were found to have <jats:italic>COL3A1<\/jats:italic> variants. Two patients with a clinical diagnosis of Loeys\u2013Dietz syndrome and\/or familial thoracic aortic aneurysm and dissection were also found to have <jats:italic>COL3A1<\/jats:italic> variants. Twenty cases (57.1%) had missense variants leading to glycine (Gly) substitutions in the triple helical domain, one (2.9%) had a missense variant leading to non\u2010Gly substitution in this domain, eight (22.9%) had splice site alterations, three (8.6%) had nonsense variants, two (5.7%) had in\u2010frame deletions, and one (2.9%) had a multi\u2010exon deletion, including two deceased patients analyzed with formalin\u2010fixed and paraffin\u2010embedded samples. This is a clinically useful system to detect a wide spectrum of variants from various types of samples.<\/jats:p>","DOI":"10.1002\/ajmg.a.62982","type":"journal-article","created":{"date-parts":[[2022,10,3]],"date-time":"2022-10-03T10:45:59Z","timestamp":1664793959000},"page":"37-51","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Comprehensive genetic screening for vascular Ehlers\u2013Danlos syndrome through an amplification\u2010based next\u2010generation sequencing system"],"prefix":"10.1002","volume":"191","author":[{"given":"Tomomi","family":"Yamaguchi","sequence":"first","affiliation":[{"name":"Department of Medical Genetics Shinshu University School of Medicine  Matsumoto Japan"},{"name":"Center for Medical Genetics Shinshu University Hospital  Matsumoto Japan"},{"name":"Division of Clinical Sequencing Shinshu University School of Medicine  Matsumoto 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