{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:09:55Z","timestamp":1771459795572,"version":"3.50.1"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T00:00:00Z","timestamp":1689292800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004191","name":"Novo Nordisk","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004191","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) have introduced an internationally shared framework for variant classification in genetic disorders. FVII deficiency is a rare inherited autosomal recessive bleeding disorder with sparse data concerning ACMG classification.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To develop an approach which may improve the utility of molecular genetic test results, 129 patients with FVII deficiency were retrospectively assigned to six subgroups for exploratory analysis: <jats:italic>F7<\/jats:italic> gene wildtype <jats:italic>(group 1)<\/jats:italic>, ACMG 1 (benign variant) or ACMG 2 (likely benign variant), only <jats:italic>(group 2)<\/jats:italic>, ACMG 3 (variant of uncertain significance) \u00b1 ACMG 1\u20132 heterozygous or not classified variant <jats:italic>(group 3)<\/jats:italic>, ACMG 4 (likely pathogenic variant), or ACMG 5 (pathogenic variant) single heterozygous \u00b1 ACMG 1\u20133 single heterozygous <jats:italic>(group 4)<\/jats:italic>, ACMG 4\u20135 homozygous or \u22652 ACMG 4\u20135 heterozygous or \u22651 ACMG 4\u20135 heterozygous plus either ACMG 1 c.1238G&amp;gt;A modifying variant homozygous or \u22652 ACMG 1\u20133 <jats:italic>(group 5)<\/jats:italic>, FVII deficiency and another bleeding disorder <jats:italic>(group 6)<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Eleven of 31 patients (35.5%) in group 5 had abnormal ISTH-BS (<jats:italic>n<\/jats:italic> = 7) and\/or history of substitution with recombinant factor VIIa (<jats:italic>n<\/jats:italic> = 5) versus 4 of 80 patients (5.0%, <jats:italic>n<\/jats:italic> = 1 abnormal ISTH-BS, <jats:italic>n<\/jats:italic> = 3 substitution) in groups 1 (<jats:italic>n<\/jats:italic> = 2\/22), 2 (<jats:italic>n<\/jats:italic> = 1\/29), 3 (<jats:italic>n<\/jats:italic> = 0\/9), and 4 (<jats:italic>n<\/jats:italic> = 1\/20). Four of 18 patients (22.2%) with FVII deficiency and another bleeding disorder (group 6) had an abnormal ISTH-BS (<jats:italic>n<\/jats:italic> = 2) and\/or history of substitution with recombinant factor VIIa (<jats:italic>n<\/jats:italic> = 3).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Patients with a homozygous ACMG 4\u20135 variant or with specific combinations of heterozygous ACMG 4\u20135 \u00b1 ACMG 1\u20133 variants exhibited a high-risk bleeding phenotype in contrast to the remaining patients without another bleeding disorder. This result may serve as a basis to develop a genotype\/phenotype prediction model in future studies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2023.1220813","type":"journal-article","created":{"date-parts":[[2023,7,15]],"date-time":"2023-07-15T08:43:51Z","timestamp":1689410631000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Utility of ACMG classification to support interpretation of molecular genetic test results in patients with factor VII deficiency"],"prefix":"10.3389","volume":"10","author":[{"given":"Rosa Sonja","family":"Alesci","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carola","family":"Hecking","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Rack\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Detlev","family":"Janssen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carl-Erik","family":"Dempfle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,7,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm6040038","article-title":"Factor FVII deficiency: clinical phenotype, genotype and therapy.","volume":"6","author":"Napolitano","year":"2017","journal-title":"J Clin Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1111\/j.1365-2516.2008.01910.x","article-title":"Greifswald Factor FVII Deficiency Study Group. 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