{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T06:45:22Z","timestamp":1787813122337,"version":"build-2784847793"},"reference-count":21,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,2,19]],"date-time":"2016-02-19T00:00:00Z","timestamp":1455840000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100006306","name":"Sigrid Jus\u00e9liuksen S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006306","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005633","name":"Syd\u00e4ntutkimuss\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003125","name":"Suomen Kulttuurirahasto","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003125","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007083","name":"Orionin Tutkimuss\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007083","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007634","name":"Ida Montinin S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007634","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2016,7]]},"abstract":"Dilated cardiomyopathy (DCM<\/jats:styled-content>), a genetically heterogeneous cardiac disease characterized by left ventricular dilatation and systolic dysfunction, is caused majorly by truncations of titin (TTN<\/jats:styled-content><\/jats:italic>), especially in A\u2010band region. Clinical interpretation of TTN<\/jats:styled-content><\/jats:italic>\u2010truncating variants (TTNtv<\/jats:styled-content>) has been challenged by the existing inaccurate variant assessment strategies and uncertainty in the true frequency of TTNtv<\/jats:styled-content> across the general population. We aggregated TTNtv<\/jats:styled-content> identified in 1788 DCM<\/jats:styled-content> patients and compared the variants with those reported in over 60,000 Exome Aggregation Consortium reference population. We implemented our current variant assessment strategy that prioritizes TTNtv<\/jats:styled-content> affecting all transcripts of the gene, and observed a decline in the prevalence of TTNtv<\/jats:styled-content> in DCM<\/jats:styled-content>. Despite this decline, TTNtv<\/jats:styled-content> are more prevalent in DCM<\/jats:styled-content> patients compared with reference population (p = 4.1 \u00d7 10\u2212295<\/jats:sup>). Moreover, our extended analyses confirmed the enrichment of TTNtv<\/jats:styled-content> not only in the A\u2010band but also in the I\/A\u2010band junction of TTN<\/jats:styled-content><\/jats:italic>. We estimated the probability of pathogenicity of TTNtv<\/jats:styled-content> affecting all transcripts of TTN<\/jats:styled-content><\/jats:italic>, identified in unselected DCM<\/jats:styled-content> patients to be 97.8% (likelihood ratio (LR) = 42.2). We emphasize that identifying a TTNtv<\/jats:styled-content>, especially in the A\u2010band region, has a higher risk of being disease\u2010causing than previously anticipated, and recommend prioritizing TTNtv<\/jats:styled-content> affecting at least five transcripts of the gene.<\/jats:p>","DOI":"10.1111\/cge.12741","type":"journal-article","created":{"date-parts":[[2016,1,18]],"date-time":"2016-01-18T13:19:15Z","timestamp":1453123155000},"page":"49-54","source":"Crossref","is-referenced-by-count":55,"title":["Relevance of truncating titin mutations in dilated cardiomyopathy"],"prefix":"10.1111","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6797-6353","authenticated-orcid":false,"given":"O.","family":"Akinrinade","sequence":"first","affiliation":[{"name":"Children's Hospital Helsinki, Pediatric Cardiology University of Helsinki and Helsinki University Central Hospital Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.\u2010P.","family":"Alastalo","sequence":"additional","affiliation":[{"name":"Children's Hospital Helsinki, Pediatric Cardiology University of Helsinki and Helsinki University Central Hospital Helsinki Finland"},{"name":"Blueprint Genetics Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.W.","family":"Koskenvuo","sequence":"additional","affiliation":[{"name":"Blueprint Genetics Helsinki Finland"},{"name":"Department of Clinical Physiology and Nuclear Medicine, HUS Medical Imaging Center Helsinki University Central Hospital and University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,2,19]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.80.3.564"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-4975(01)02784-9"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/415227a"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genom.6.080604.162132"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/HCO.0b013e328337ba52"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200012073432304"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1752-8062.2010.00198.x"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehv253"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1110186"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3010134"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehu301"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.112.962928"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09534"},{"key":"e_1_2_6_15_1","unstructured":""},{"key":"e_1_2_6_16_1","unstructured":""},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0145284"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng815"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.111.000062"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1215040"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.115.002645"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2009.04.014"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcge.12741","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.12741","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T06:57:15Z","timestamp":1696316235000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.12741"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2,19]]},"references-count":21,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2016,7]]}},"alternative-id":["10.1111\/cge.12741"],"URL":"https:\/\/doi.org\/10.1111\/cge.12741","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2,19]]}}}