{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T07:49:19Z","timestamp":1753861759900,"version":"3.41.2"},"reference-count":25,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T00:00:00Z","timestamp":1698019200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Clinical interpretation of genetic variants in the context of the patient's phenotype is a time\u2010consuming and costly process. In\u2010silico analysis using in\u2010silico prediction tools, and molecular modeling have been developed to predict the influence of genetic variants on the quality and\/or quantity of the resulting translated protein, and in this way, to alert clinicians of disease likelihood in the absence of previous evidence. Our objectives were to evaluate the success rate of the in\u2010silico analysis in predicting the disease\u2010causing variants as pathogenic and the single\u2010nucleotide variants as neutral, and to establish the reliability of in\u2010silico analysis for determining pathogenicity or neutrality of von Willebrand factor gene\u2010associated genetic variants. Using in\u2010silico analysis, we studied pathogenicity in 31 disease\u2010causing variants, and neutrality in 61 single\u2010nucleotide variants from patients previously diagnosed as type 2 von Willebrand disease. Disease\u2010causing variants and non\u2010synonymous single\u2010nucleotide variants were explored by in\u2010silico tools that analyze the amino acidic sequence. Intronic and synonymous single\u2010nucleotide variants were analyzed by in\u2010silico methods that evaluate the nucleotidic sequence. We found a consistent agreement between predictions achieved by in\u2010silico prediction tools and molecular modeling, both for defining the pathogenicity of disease\u2010causing variants and the neutrality of single\u2010nucleotide variants. Based on our results, the in\u2010silico analysis would help to define the pathogenicity or neutrality in novel genetic variants observed in patients with clinical and laboratory phenotypes suggestive of von Willebrand disease.<\/jats:p>","DOI":"10.1002\/ajmg.a.63430","type":"journal-article","created":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T04:48:53Z","timestamp":1698122933000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Clinical relevance of genetic variants in the von Willebrand factor according to in\u2010silico methods"],"prefix":"10.1002","volume":"194","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4077-1796","authenticated-orcid":false,"given":"Adriana In\u00e9s","family":"Woods","sequence":"first","affiliation":[{"name":"Laboratorio de Hemostasia y Trombosis IMEX\u2010CONICET\u2010Academia Nacional de Medicina de Buenos Aires  CABA Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7370-1073","authenticated-orcid":false,"given":"D\u00e9bora Marina","family":"Primrose","sequence":"additional","affiliation":[{"name":"Escuela Superior de Ingenier\u00eda, Inform\u00e1tica y Ciencias Agroalimentarias, Universidad de Mor\u00f3n  Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2083-1269","authenticated-orcid":false,"given":"Juvenal","family":"Paiva","sequence":"additional","affiliation":[{"name":"Departamento de Hemostasia y Trombosis Instituto de Investigaciones Hematol\u00f3gicas, Academia Nacional de Medicina de Buenos Aires  CABA Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6933-1057","authenticated-orcid":false,"given":"Alicia Noem\u00ed","family":"Blanco","sequence":"additional","affiliation":[{"name":"Departamento de Hemostasia y Trombosis Instituto de Investigaciones Hematol\u00f3gicas, Academia Nacional de Medicina de Buenos Aires  CABA Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7048-2031","authenticated-orcid":false,"given":"Mar\u00eda Fabiana","family":"Alberto","sequence":"additional","affiliation":[{"name":"Departamento de Hemostasia y Trombosis Instituto de Investigaciones Hematol\u00f3gicas, Academia Nacional de Medicina de Buenos Aires  CABA Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2971-9217","authenticated-orcid":false,"given":"Anal\u00eda","family":"S\u00e1nchez\u2010Luceros","sequence":"additional","affiliation":[{"name":"Laboratorio de Hemostasia y Trombosis IMEX\u2010CONICET\u2010Academia Nacional de Medicina de Buenos Aires  CABA Argentina"},{"name":"Departamento de Hemostasia y Trombosis Instituto de Investigaciones Hematol\u00f3gicas, Academia Nacional de Medicina de Buenos Aires  CABA Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,10,23]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.03.024"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-017-0508-z"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-10-384610"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH06-03-0144"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.13366"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-019-6413-7"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13040-021-00244-z"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu733"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23158"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-017-1353-5"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-42059-2_1"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2892"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12008"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1053\/beha.2001.0138"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1099-1352(199601)9:1<1::aid-jmr241>3.0.co;2-6"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0119420"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-987X(19981115)19:14<1639:AID-JCC10>3.0.CO;2-B"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2007.01643.x"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V69.2.454.454"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2006.02146.x"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12733"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0022-3476(05)80384-1"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0041-1726097"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2020.11.029"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-01-405134"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.63430","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,13]],"date-time":"2024-02-13T09:55:30Z","timestamp":1707818130000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.63430"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,23]]},"references-count":25,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1002\/ajmg.a.63430"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.63430","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"type":"print","value":"1552-4825"},{"type":"electronic","value":"1552-4833"}],"subject":[],"published":{"date-parts":[[2023,10,23]]},"assertion":[{"value":"2023-04-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e63430"}}