{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T13:13:24Z","timestamp":1792761204469,"version":"4.5.0"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T00:00:00Z","timestamp":1724025600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T00:00:00Z","timestamp":1724025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004329","name":"Javna Agencija za Raziskovalno Dejavnost RS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J. Cardiovasc. Transl. Res."],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Hypertrophic cardiomyopathy is often caused by pathogenic <jats:italic>MYBPC3<\/jats:italic> variants. The study of Italian patients with HCM and <jats:italic>MYBPC3<\/jats:italic>(NM_000256.3):c.913_914del showed a higher disease penetrance in males and a higher frequency of arrhythmias compared to patients with other likely pathogenic and pathogenic (LP\/P) <jats:italic>MYBPC3<\/jats:italic> variants. We investigated the clinical outcomes of Slovenian probands with <jats:italic>MYBPC3<\/jats:italic> LP\/P variants, estimated the variant penetrance and compared the results with an Italian study. We identified 31 haplotype-matched individuals with <jats:italic>MYBPC3<\/jats:italic>:c.913_914del and 34 individuals with other LP\/P <jats:italic>MYBPC3<\/jats:italic> variants. We observed some significant differences in clinical and echocardiographic characteristics and frequency of adverse cardiac events between Slovenian and Italian probands with <jats:italic>MYBPC3<\/jats:italic>:c913_914del. We were unable to replicate previous findings for <jats:italic>MYBPC3<\/jats:italic>:c.913_914del, highlighting the complexity of genotype\u2013phenotype associations.<\/jats:p>\n          <jats:p>\n            <jats:bold>Graphical Abstract<\/jats:bold>\n          <\/jats:p>","DOI":"10.1007\/s12265-024-10551-5","type":"journal-article","created":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T20:13:47Z","timestamp":1724098427000},"page":"110-120","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Clinical Outcome of Hypertrophic Cardiomyopathy in Probands with the Founder Variant c.913_914del in MYBPC3: A Slovenian Cohort Study"],"prefix":"10.1007","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5659-2437","authenticated-orcid":false,"given":"Nina","family":"Vodnjov","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9826-0534","authenticated-orcid":false,"given":"Ale\u0161","family":"Maver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nata\u0161a","family":"Teran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7824-4978","authenticated-orcid":false,"given":"Borut","family":"Peterlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3272-1641","authenticated-orcid":false,"given":"Janez","family":"Topli\u0161ek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0388-5361","authenticated-orcid":false,"given":"Karin","family":"Writzl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,8,19]]},"reference":[{"key":"10551_CR1","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.1016\/j.jacc.2015.01.019","volume":"65","author":"C Semsarian","year":"2015","unstructured":"Semsarian C, Ingles J, Maron MS, Maron BJ. New Perspectives on the Prevalence of Hypertrophic Cardiomyopathy. J Am Coll Cardiol. 2015;65:1249\u201354. https:\/\/doi.org\/10.1016\/j.jacc.2015.01.019.","journal-title":"J Am Coll Cardiol"},{"key":"10551_CR2","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1002\/joa3.12717","volume":"38","author":"AAM Wilde","year":"2022","unstructured":"Wilde AAM, Semsarian C, M\u00e1rquez MF, et al. European Heart Rhythm Association (EHRA)\/Heart Rhythm Society (HRS)\/Asia Pacific Heart Rhythm Society (APHRS)\/Latin American Heart Rhythm Society (LAHRS) Expert Consensus Statement on the state of genetic testing for cardiac diseases. J Arrhythm. 2022;38:491\u2013553. https:\/\/doi.org\/10.1002\/joa3.12717.","journal-title":"J Arrhythm"},{"issue":"37","key":"10551_CR3","doi-asserted-by":"publisher","first-page":"3503","DOI":"10.1093\/eurheartj\/ehad194","volume":"44","author":"E Arbelo","year":"2023","unstructured":"Arbelo E, Protonotarios A, Gimeno JR, et al. 2023 ESC Guidelines for the management of cardiomyopathies. Eur Heart J. 2023;44(37):3503\u2013626. https:\/\/doi.org\/10.1093\/eurheartj\/ehad194.","journal-title":"Eur Heart J."},{"key":"10551_CR4","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1002\/1873-3468.14301","volume":"596","author":"C Suay-Corredera","year":"2022","unstructured":"Suay-Corredera C, Alegre-Cebollada J. The mechanics of the heart: zooming in on hypertrophic cardiomyopathy and cMyBP-C. FEBS Lett. 2022;596:703\u201346. https:\/\/doi.org\/10.1002\/1873-3468.14301.","journal-title":"FEBS Lett"},{"key":"10551_CR5","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1007\/s10974-012-9291-z","volume":"33","author":"M Pfuhl","year":"2012","unstructured":"Pfuhl M, Gautel M. Structure, interactions and function of the N-terminus of cardiac myosin binding protein C (MyBP-C): who does what, with what, and to whom? J Muscle Res Cell Motil. 2012;33:83\u201394. https:\/\/doi.org\/10.1007\/s10974-012-9291-z.","journal-title":"J Muscle Res Cell Motil"},{"key":"10551_CR6","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1038\/ng1295-438","volume":"11","author":"G Bonne","year":"1995","unstructured":"Bonne G, Carrier L, Bercovici J, et al. Cardiac myosin binding protein\u2013C gene splice acceptor site mutation is associated with familial hypertrophic cardiomyopathy. Nat Genet. 1995;11:438\u201340. https:\/\/doi.org\/10.1038\/ng1295-438.","journal-title":"Nat Genet"},{"key":"10551_CR7","doi-asserted-by":"publisher","first-page":"e001620","DOI":"10.1161\/CIRCGENETICS.116.001620","volume":"10","author":"J Ingles","year":"2017","unstructured":"Ingles J, Burns C, Bagnall RD, et al. Nonfamilial Hypertrophic Cardiomyopathy: Prevalence, Natural History, and Clinical Implications. Circ Cardiovasc Genet. 2017;10:e001620. https:\/\/doi.org\/10.1161\/CIRCGENETICS.116.001620.","journal-title":"Circ Cardiovasc Genet"},{"key":"10551_CR8","doi-asserted-by":"publisher","first-page":"e001815","DOI":"10.1136\/openhrt-2021-001815","volume":"9","author":"S Christian","year":"2022","unstructured":"Christian S, Cirino A, Hansen B, et al. Diagnostic validity and clinical utility of genetic testing for hypertrophic cardiomyopathy: a systematic review and meta-analysis. Open Heart. 2022;9:e001815. https:\/\/doi.org\/10.1136\/openhrt-2021-001815.","journal-title":"Open Heart"},{"key":"10551_CR9","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1161\/CIRCGEN.122.003832","volume":"16","author":"M Beltrami","year":"2023","unstructured":"Beltrami M, Fedele E, Fumagalli C, et al. Long-Term Prevalence of Systolic Dysfunction in MYBPC3 Versus MYH7-Related Hypertrophic Cardiomyopathy. Circ Genom Precis Med. 2023;16:363\u201371. https:\/\/doi.org\/10.1161\/CIRCGEN.122.003832.","journal-title":"Circ Genom Precis Med"},{"key":"10551_CR10","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1136\/jmedgenet-2014-102923","volume":"52","author":"C Calore","year":"2015","unstructured":"Calore C, De Bortoli M, Romualdi C, et al. A founder MYBPC3 mutation results in HCM with a high risk of sudden death after the fourth decade of life. J Med Genet. 2015;52:338\u201347. https:\/\/doi.org\/10.1136\/jmedgenet-2014-102923.","journal-title":"J Med Genet"},{"key":"10551_CR11","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1038\/gim.2016.22","volume":"18","author":"A Maver","year":"2016","unstructured":"Maver A, Lovrecic L, Volk M, et al. Phenotype-driven gene target definition in clinical genome-wide sequencing data interpretation. Genet Med. 2016;18:1102\u201310. https:\/\/doi.org\/10.1038\/gim.2016.22.","journal-title":"Genet Med"},{"key":"10551_CR12","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1038\/gim.2017.142","volume":"20","author":"G Bergant","year":"2018","unstructured":"Bergant G, Maver A, Lovrecic L, et al. Comprehensive use of extended exome analysis improves diagnostic yield in rare disease: a retrospective survey in 1,059 cases. Genet Med. 2018;20:303\u201312. https:\/\/doi.org\/10.1038\/gim.2017.142.","journal-title":"Genet Med"},{"key":"10551_CR13","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1038\/s41531-022-00408-6","volume":"8","author":"A Kovanda","year":"2022","unstructured":"Kovanda A, Ra\u010dki V, Bergant G, et al. A multicenter study of genetic testing for Parkinson\u2019s disease in the clinical setting. NPJ Parkinsons Dis. 2022;8:149. https:\/\/doi.org\/10.1038\/s41531-022-00408-6.","journal-title":"NPJ Parkinsons Dis"},{"key":"10551_CR14","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","volume":"17","author":"S Richards","year":"2015","unstructured":"Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17:405\u201324. https:\/\/doi.org\/10.1038\/gim.2015.30.","journal-title":"Genet Med"},{"key":"10551_CR15","unstructured":"Ellard S, Baple EL, Callaway A, et al. ACGS best practice guidelines for variant classification in rare disease 2020. 2020. Available online: https:\/\/www.acgs.uk.Com\/media\/11631\/uk-practice-guidelines-for-variant-classification-v4-01-2020.pdf. Accessed 30 July 2024."},{"key":"10551_CR16","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1038\/nbt.1754","volume":"29","author":"JT Robinson","year":"2011","unstructured":"Robinson JT, Thorvaldsd\u00f3ttir H, Winckler W, et al. Integrative genomics viewer. Nat Biotechnol. 2011;29:24\u20136. https:\/\/doi.org\/10.1038\/nbt.1754.","journal-title":"Nat Biotechnol"},{"key":"10551_CR17","doi-asserted-by":"publisher","first-page":"e558","DOI":"10.1161\/CIR.0000000000000937","volume":"142","author":"SR Ommen","year":"2020","unstructured":"Writing Committee Members, Ommen SR, Mital S, et al. 2020 AHA\/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy: A Report of the American College of Cardiology\/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2020;142:e558\u2013631. https:\/\/doi.org\/10.1161\/CIR.0000000000000937.","journal-title":"Circulation"},{"key":"10551_CR18","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/j.echo.2016.01.011","volume":"29","author":"SF Nagueh","year":"2016","unstructured":"Nagueh SF, Smiseth OA, Appleton CP, et al. Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2016;29:277\u2013314. https:\/\/doi.org\/10.1016\/j.echo.2016.01.011.","journal-title":"J Am Soc Echocardiogr"},{"key":"10551_CR19","doi-asserted-by":"publisher","first-page":"2733","DOI":"10.1093\/eurheartj\/ehu284","volume":"35","author":"C Muneretto","year":"2014","unstructured":"Muneretto C, Elliott P, Anastasakis A, Borger M, Borggrefe M, Cecchi F, Charron P, Hagege A, Lafont A, Limongelli G, Mahrholdt H. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: The Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur Heart J. 2014;35:2733\u201379. https:\/\/doi.org\/10.1093\/eurheartj\/ehu284.","journal-title":"Eur Heart J"},{"key":"10551_CR20","unstructured":"HCM Risk-SCD. https:\/\/qxmd.com\/calculate\/calculator_303\/hcm-risk-scd. Accessed 18 Dec 2023"},{"key":"10551_CR21","doi-asserted-by":"publisher","first-page":"D1062","DOI":"10.1093\/nar\/gkx1153","volume":"46","author":"MJ Landrum","year":"2018","unstructured":"Landrum MJ, Lee JM, Benson M, et al. ClinVar: improving access to variant interpretations and supporting evidence. Nucleic Acids Res. 2018;46:D1062\u20137. https:\/\/doi.org\/10.1093\/nar\/gkx1153.","journal-title":"Nucleic Acids Res"},{"key":"10551_CR22","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1002\/humu.21438","volume":"32","author":"IFAC Fokkema","year":"2011","unstructured":"Fokkema IFAC, Taschner PEM, Schaafsma GCP, et al. LOVD vol 2.0: the next generation in gene variant databases. Hum Mutat. 2011;32:557\u201363. https:\/\/doi.org\/10.1002\/humu.21438.","journal-title":"Hum Mutat"},{"key":"10551_CR23","doi-asserted-by":"publisher","first-page":"630","DOI":"10.4065\/83.6.630","volume":"83","author":"I Olivotto","year":"2008","unstructured":"Olivotto I, Girolami F, Ackerman MJ, et al. Myofilament protein gene mutation screening and outcome of patients with hypertrophic cardiomyopathy. Mayo Clin Proc. 2008;83:630\u20138. https:\/\/doi.org\/10.4065\/83.6.630.","journal-title":"Mayo Clin Proc"},{"key":"10551_CR24","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.1038\/ejhg.2017.109","volume":"25","author":"M De Bortoli","year":"2017","unstructured":"De Bortoli M, Calore C, Lorenzon A, et al. Co-inheritance of mutations associated with arrhythmogenic cardiomyopathy and hypertrophic cardiomyopathy. Eur J Hum Genet. 2017;25:1165\u20139. https:\/\/doi.org\/10.1038\/ejhg.2017.109.","journal-title":"Eur J Hum Genet"},{"key":"10551_CR25","doi-asserted-by":"publisher","first-page":"e001671","DOI":"10.1161\/CIRCGENETICS.116.001671","volume":"10","author":"SB Ross","year":"2017","unstructured":"Ross SB, Bagnall RD, Ingles J, et al. Burden of Recurrent and Ancestral Mutations in Families With Hypertrophic Cardiomyopathy. Circ Cardiovasc Genet. 2017;10:e001671. https:\/\/doi.org\/10.1161\/CIRCGENETICS.116.001671.","journal-title":"Circ Cardiovasc Genet"},{"key":"10551_CR26","doi-asserted-by":"publisher","first-page":"e001660","DOI":"10.1161\/CIRCGENETICS.116.001660","volume":"10","author":"HG van Velzen","year":"2017","unstructured":"van Velzen HG, Schinkel AFL, Oldenburg RA, et al. Clinical Characteristics and Long-Term Outcome of Hypertrophic Cardiomyopathy in Individuals With a MYBPC3 (Myosin-Binding Protein C) Founder Mutation. Circ Cardiovasc Genet. 2017;10:e001660. https:\/\/doi.org\/10.1161\/CIRCGENETICS.116.001660.","journal-title":"Circ Cardiovasc Genet"},{"key":"10551_CR27","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1038\/gim.2016.90","volume":"19","author":"R Walsh","year":"2017","unstructured":"Walsh R, Thomson KL, Ware JS, et al. Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples. Genet Med. 2017;19:192\u2013203. https:\/\/doi.org\/10.1038\/gim.2016.90.","journal-title":"Genet Med"},{"key":"10551_CR28","doi-asserted-by":"publisher","first-page":"24691","DOI":"10.1073\/pnas.2006764117","volume":"117","author":"T Tucholski","year":"2020","unstructured":"Tucholski T, Cai W, Gregorich ZR, et al. Distinct hypertrophic cardiomyopathy genotypes result in convergent sarcomeric proteoform profiles revealed by top-down proteomics. Proc Natl Acad Sci USA. 2020;117:24691\u2013700. https:\/\/doi.org\/10.1073\/pnas.2006764117.","journal-title":"Proc Natl Acad Sci USA"},{"key":"10551_CR29","doi-asserted-by":"publisher","first-page":"2441","DOI":"10.1161\/CIRCULATIONAHA.110.954446","volume":"122","author":"AP Landstrom","year":"2010","unstructured":"Landstrom AP, Ackerman MJ. Mutation Type Is Not Clinically Useful in Predicting Prognosis in Hypertrophic Cardiomyopathy. Circulation. 2010;122:2441\u201350. https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.110.954446.","journal-title":"Circulation"},{"key":"10551_CR30","doi-asserted-by":"publisher","first-page":"1482","DOI":"10.1016\/j.ajhg.2023.08.003","volume":"110","author":"KA McGurk","year":"2023","unstructured":"McGurk KA, Zhang X, Theotokis P, et al. The penetrance of rare variants in cardiomyopathy-associated genes: A cross-sectional approach to estimating penetrance for secondary findings. Am J Human Genet. 2023;110:1482\u201395. https:\/\/doi.org\/10.1016\/j.ajhg.2023.08.003.","journal-title":"Am J Human Genet"},{"key":"10551_CR31","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1186\/s13073-022-01142-7","volume":"14","author":"TP Spargo","year":"2022","unstructured":"Spargo TP, Opie-Martin S, Bowles H, et al. Calculating variant penetrance from family history of disease and average family size in population-scale data. Genome Med. 2022;14:141. https:\/\/doi.org\/10.1186\/s13073-022-01142-7.","journal-title":"Genome Med"}],"container-title":["Journal of Cardiovascular Translational Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12265-024-10551-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12265-024-10551-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12265-024-10551-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T14:41:56Z","timestamp":1741272116000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12265-024-10551-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,19]]},"references-count":31,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10551"],"URL":"https:\/\/doi.org\/10.1007\/s12265-024-10551-5","relation":{},"ISSN":["1937-5387","1937-5395"],"issn-type":[{"value":"1937-5387","type":"print"},{"value":"1937-5395","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,19]]},"assertion":[{"value":"21 November 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 July 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 August 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study followed the Declaration of Helsinki and was approved by the National Medical Ethics Committee of Slovenia (0120\u201371\/2022\/3). All participants provided written consent and were anonymized using specific codes as part of standard diagnostic procedures.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed Consent"}},{"value":"The authors declare no competing interests. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}]}}