{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T22:09:47Z","timestamp":1785362987591,"version":"3.55.0"},"reference-count":72,"publisher":"Oxford University Press (OUP)","issue":"21","license":[{"start":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T00:00:00Z","timestamp":1724112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["331946"],"award-info":[{"award-number":["331946"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Finnish Cancer Foundation"},{"name":"Sigrid Juselius Foundation and Finnish Foundation for Cardiovascular Research"},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK Program","doi-asserted-by":"crossref","award":["CRUK-A21671"],"award-info":[{"award-number":["CRUK-A21671"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003502","name":"Ella and Georg Ehrnrooth Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003502","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Variants of talin-1 (TLN1) have recently been linked with spontaneous coronary artery dissection (SCAD) a condition where a tear can form in the wall of a heart artery necessitating immediate medical care. One talin-1 variant, A2013T, has an extensive familial pedigree of SCAD, which led to the screening for, and identification of, further talin-1 variants in SCAD patients. Here we evaluated these variants with commonly used pathogenicity prediction tools and found it challenging to reliably classify SCAD-associated variants, even A2013T where the evidence of a causal role is strong. Using biochemical and cell biological methods, we show that SCAD-associated variants in talin-1, which would typically be classified as non-pathogenic, still cause a measurable impact on protein structure and cell behaviour, including cell movement and wound healing capacity. Together, this indicates that even subtle variants in central mechanosensitive adapter proteins, can give rise to significant health impacts at the individual level, suggesting the need for a possible re-evaluation of the scoring criteria for pathogenicity prediction for talin variants.<\/jats:p>","DOI":"10.1093\/hmg\/ddae120","type":"journal-article","created":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T07:41:36Z","timestamp":1730965296000},"page":"1846-1857","source":"Crossref","is-referenced-by-count":5,"title":["Talin-1 variants associated with spontaneous coronary artery dissection (SCAD) highlight how even subtle changes in multi-functional scaffold proteins can manifest in disease"],"prefix":"10.1093","volume":"33","author":[{"given":"Latifeh","family":"Azizi","sequence":"first","affiliation":[{"name":"Faculty of Medicine and Health Technology, Tampere University , Arvo Ylp\u00f6n katu, 33520 Tampere,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasumi","family":"Otani","sequence":"additional","affiliation":[{"name":"Department of Biochemistry , Cell & Systems Biology, , Crown Street, Liverpool L69 7ZB,","place":["United States"]},{"name":"Institute of Systems, Molecular & Integrative Biology, University of Liverpool , Cell & Systems Biology, , Crown Street, Liverpool L69 7ZB,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasyl V","family":"Mykuliak","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Technology, Tampere University , Arvo Ylp\u00f6n katu, 33520 Tampere,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin T","family":"Goult","sequence":"additional","affiliation":[{"name":"Department of Biochemistry , Cell & Systems Biology, , Crown Street, Liverpool L69 7ZB,","place":["United States"]},{"name":"Institute of Systems, Molecular & Integrative Biology, University of Liverpool , Cell & Systems Biology, , Crown Street, Liverpool L69 7ZB,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9357-1480","authenticated-orcid":false,"given":"Vesa P","family":"Hyt\u00f6nen","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Technology, Tampere University , Arvo Ylp\u00f6n katu, 33520 Tampere,","place":["Finland"]},{"name":"Fimlab Laboratories , Biokatu 4, 33520 Tampere,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5969-4807","authenticated-orcid":false,"given":"Paula","family":"Turkki","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Technology, Tampere University , Arvo Ylp\u00f6n katu, 33520 Tampere,","place":["Finland"]},{"name":"Fimlab Laboratories , Biokatu 4, 33520 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