{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T12:27:22Z","timestamp":1763728042642,"version":"3.40.4"},"reference-count":38,"publisher":"S. Karger AG","issue":"6","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cardiology"],"published-print":{"date-parts":[[2021]]},"abstract":"<jats:p>&lt;b&gt;&lt;i&gt;Introduction:&lt;\/i&gt;&lt;\/b&gt; Whether detailed genetic information contributes to risk stratification of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) remains uncertain. Pathogenic genetic variants in some genes seem to carry a higher risk for arrhythmia and earlier disease onset than others, but comparisons between variants in the same gene have not been done. Combined Annotation Dependent Depletion (CADD) score is a bioinformatics tool that measures the pathogenicity of each genetic variant. We hypothesized that a higher CADD score is associated with arrhythmic events and earlier age at ARVC manifestations in individuals carrying pathogenic or likely pathogenic genetic variants in plakophilin-2 (&lt;i&gt;PKP2&lt;\/i&gt;). &lt;b&gt;&lt;i&gt;Methods:&lt;\/i&gt;&lt;\/b&gt; CADD scores were calculated using the data from pooled Scandinavian and North American ARVC cohorts, and their association with cardiac events defined as ventricular tachycardia\/ventricular fibrillation (VT\/VF) or syncope and age at definite ARVC diagnosis were assessed. &lt;b&gt;&lt;i&gt;Results:&lt;\/i&gt;&lt;\/b&gt; In total, 33 unique genetic variants were reported in 179 patients (90 males, 71 probands, 96 with definite ARVC diagnosis at a median age of 35 years). Cardiac events were reported in 76 individuals (43%), of whom 53 had sustained VT\/VF (35%). The CADD score was neither associated with age at cardiac events (HR 1.002, 95% CI: 0.953\u20131.054, &lt;i&gt;p&lt;\/i&gt; = 0.933) nor with age at definite ARVC diagnosis (HR 0.992, 95% CI: 0.947\u20131.039, &lt;i&gt;p&lt;\/i&gt; = 0.731). &lt;b&gt;&lt;i&gt;Conclusion:&lt;\/i&gt;&lt;\/b&gt; No correlation was found between CADD scores and clinical manifestations of ARVC, indicating that the score has no additional risk stratification value among carriers of pathogenic or likely pathogenic &lt;i&gt;PKP2&lt;\/i&gt; genetic variants. <\/jats:p>","DOI":"10.1159\/000519231","type":"journal-article","created":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T21:00:32Z","timestamp":1630530032000},"page":"763-771","source":"Crossref","is-referenced-by-count":4,"title":["Genetic Variant Score and Arrhythmogenic Right Ventricular Cardiomyopathy Phenotype in Plakophilin-2 Mutation Carriers"],"prefix":"10.1159","volume":"146","author":[{"given":"Anneli","family":"Svensson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pyotr G.","family":"Platonov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristina H.","family":"Haugaa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wojciech","family":"Zareba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henrik 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