caa a22 4500 605479046 CHVBK 20210128100408.0 cr unu---uuuuu 210128e20150901xx s 000 0 eng 10.1007/s10741-015-9495-6 doi (NATIONALLICENCE)springer-10.1007/s10741-015-9495-6 Titin mutations: the fall of Goliath [Elektronische Daten] [Manuel Neiva-Sousa, João Almeida-Coelho, Inês Falcão-Pires, Adelino Leite-Moreira] Titin (TTN), the largest protein in the human body, forms powerful elastic filaments along the sarcomere of cardiomyocytes. This multifunctional protein is involved in numerous cellular processes, including sarcomeric assembly, stabilization and mechanosensing. Along physiological sarcomere lengths, TTN is also the most important determinant of the passive tension of cardiac muscle. However, as the giant Goliath was brought down by David's slingshot, so single-base-pair mutations in the gene encoding TTN (TTN) can ultimately impair to some degree a normal cardiac function. Since the first report on the involvement of TTN mutations in the development of hypertrophic cardiomyopathy, in 1999, dozens of other mutations have been described and associated with the onset of cardiac disease. In this review, we aim to explore some of the mechanisms underlying the functions of TTN, as well as the pathophysiological consequences arising from the expression of abnormal TTN isoforms resulting from mutations located along TTN. Springer Science+Business Media New York, 2015 Titin nationallicence Mutations nationallicence Cardiomyopathies nationallicence Sarcomerogenesis nationallicence Neiva-Sousa Manuel Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal aut Almeida-Coelho João Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal aut Falcão-Pires Inês Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal aut Leite-Moreira Adelino Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal aut Heart Failure Reviews Springer US; http://www.springer-ny.com 20/5(2015-09-01), 579-588 1382-4147 20:5<579 2015 20 10741 https://doi.org/10.1007/s10741-015-9495-6 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10741-015-9495-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Neiva-Sousa Manuel Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal aut NATIONALLICENCE 700 1- Almeida-Coelho João Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal aut NATIONALLICENCE 700 1- Falcão-Pires Inês Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal aut NATIONALLICENCE 700 1- Leite-Moreira Adelino Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal aut NATIONALLICENCE 773 0- Heart Failure Reviews Springer US; http://www.springer-ny.com 20/5(2015-09-01), 579-588 1382-4147 20:5<579 2015 20 10741