Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls.

Address: Department of Clinical and Experimental Cardiology, Heart Centre, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands. [email protected].; Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands. [email protected].; Department of Clinical and Experimental Cardiology, Heart Centre, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.; Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands.; Department of Medicine, Cardiovascular Genetics Center, Montreal Heart Institute and Faculty of Medicine, Université de Montréal, Montreal, QC, Canada.; Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands.; Université de Nantes, CHU Nantes, CNRS, INSERM, l'institut du thorax, Nantes, France.; Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands.; Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.; Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands.; Department of Clinical Genetics, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.; National Heart and Lung Institute, Imperial College London, London, United Kingdom.; Cardiovascular Research Centre, Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom.; MRC London Institute of Medical Sciences, Imperial College London, London, United Kingdom.; National Heart and Lung Institute, Imperial College London, London, United Kingdom.; Cardiovascular Research Centre, Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom.; Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy.; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.; Arrhythmia Section, Cardiology Department, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.; IDIBAPS, Institut d'Investigació August Pi i Sunyer (IDIBAPS), Barcelona, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain.; CHU Tours, Service de Cardiologie, Tours, France.; Lankenau Institute for Medical Research, Wynnewood, PA, USA.; Department of Internal Medicine I, LMU Klinikum, Klinikum der Ludwig Maximilians Universität München, München, Germany.; Department of Cardiovascular Medicine, Division of Heart Rhythm Services, Mayo Clinic, Rochester, MN, USA.; Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands.; Department of Human Genetics, University Hospitals Leuven, Leuven, Belgium.; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain.; Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona, Spain.; Medical Science Department, School of Medicine, University of Girona, Girona, Spain.; Biochemistry and Molecular Genetics Department, Hospital Clinic, University of Barcelona-IDIBAPS, Barcelona, Spain.; Istituto Auxologico Italiano, IRCCS-Center for Cardiac Arrhythmias of Genetic Origin, Milan, Italy.; Department of Cardiology, Ege University School of Medicine, Izmir, Turkey.; Department of Internal Medicine I, LMU Klinikum, Klinikum der Ludwig Maximilians Universität München, München, Germany.; German Centre for Cardiovascular Research (DZHK), Partner Site Munich, Munich Heart Alliance (MHA), Munich, Germany.; Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians University Munich (LMU), Munich, Germany.; Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands.; Center for Human Genetics, University Hospitals Leuven, Leuven, Belgium.; Istituto Auxologico Italiano, IRCCS-Center for Cardiac Arrhythmias of Genetic Origin, Milan, Italy.; Istituto Auxologico Italiano, IRCCS, Department of Cardiovascular, Neural and Metabolic Sciences, San Luca Hospital, Milan, Italy.; Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy.; Istituto Auxologico Italiano, IRCCS-Laboratory of Cardiovascular Genetics, Cusano Milanino, MI, Italy.; Heart Rhythm Management Center, Postgraduate program in Cardiac Electrophysiology and Pacing Universitair Ziekenhuis, Brussel-Vrije Universiteit Brussel, ERN Heart Guard Center, Brussels, Belgium.; Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands.; CNMR Maladies Cardiaques Héréditaires Rares, Hôpital Bichat, Université de Paris, Paris, France.; AP-HP, Service de Cardiologie, Hôpital Bichat, Paris, France.; Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands.; Institute for Genetics of Heart Diseases, University Hospital Münster, Münster, Germany.; Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.; Cardiovascular Disease Initiative, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.; Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands.; Cardiogenetic Laboratory, Inherited Cardiac Disease Unit, University Hospital Virgen de la Arrixaca-IMIB, Murcia, Spain.; Division of Cardiology, University of Torino, Department of Medical Sciences, "Città della Salute e della Scienza" Hospital, Torino, Italy.; Department of Pediatrics, Kagoshima City Hospital, Kagoshima, Japan.; Center for Epidemiologic Research in Asia, Shiga University of Medical Science, Seta-Tsukinowa-cho, Otsu, Japan.; Omics Research Center, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.; Division of Patient Safety, Hiroshima University Hospital, Minami-ku, Hiroshima, Japan.; Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.; Laboratory of Experimental Cardiology, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.; Department of Molecular Physiology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.; Istituto Auxologico Italiano, IRCCS-Center for Cardiac Arrhythmias of Genetic Origin, Milan, Italy.; Istituto Auxologico Italiano, IRCCS-Laboratory of Cardiovascular Genetics, Cusano Milanino, MI, Italy.; Department of Clinical Genetics, Maastricht University Medical Center+, Maastricht, Netherlands.; Department of Medicine and Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.; Center of Medical Genetics, Faculty of Medicine and Health Sciences, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium.; Department of Clinical Genetics and Pathology, Lund University, Lund, Sweden.; Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.; CHU Brest, Service de Cardiologie, Brest, France.; Univ Rennes, CHU Rennes, INSERM, Rennes, France.; Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands.; Molecular Cardiology, ICS Maugeri, IRCCS and Department of Molecular Medicine, University of Pavia, Pavia, Italy.; Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands.; Centre for Cardiovascular Genetics, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.; Department of Cardiovascular Medicine, Nihon University, Tokyo, Japan.; Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands.; Molecular and Clinical Sciences Research Institute, St. George's, University of London, London, United Kingdom.; Cardiology Clinical Academic Group, St. George's University Hospitals' NHS Foundation Trust, London, United Kingdom.; Department of Medicine, University Medical Center Mannheim, Mannheim, Germany.; German Center for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, Mannheim, Germany.; Hôpital Cardiologique du Haut-Lévêque, LIRYC Institute, Université Bordeaux, Bordeaux, France.; Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands.; Medical Science Department, School of Medicine, University of Girona, Girona, Spain.; Arrhythmias Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.; Medical Genetics, San Luigi Univesity Hospital, Orbassano, TO, Italy.; Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Cardiology and Angiology I, Heart Center University of Freiburg, Medical Faculty, Freiburg, Germany.; Department of Pediatrics, National Hospital Organization Kagoshima Medical Center, Kagoshima, Japan.; Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.; Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands.; Centre for Medical Genetics, research group Reproduction and Genetics, research cluster Reproduction, Genetics and Regenerative Medicine, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium.; Department of Physiology, University of Auckland, Auckland, New Zealand.; Department of Cardiology, CARIM, Maastricht University Medical Center+, Maastricht, Netherlands.; Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden.; Department of Cardiology and Angiology I, Heart Center University of Freiburg, Medical Faculty, Freiburg, Germany.; Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA.; Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, Western University, London, ON, Canada.; Cardiac Inherited Disease Group, Starship Childrens Hospital, Auckland, New Zealand.; Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands.; Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.; Department of Forensic Medicine, Faculty of Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.; Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.; Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands.; Barts Heart Centre, Barts Health NHS Trust & Institute of Cardiovascular Science, University College London, London, United Kingdom.; Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands.; Department of Clinical Sciences, Paediatrics, Umeå University, Umeå, Sweden.; Department of Cardiology, University of Antwerp, Antwerp University Hospital, Antwerp, Belgium.; Department of Internal Medicine I, LMU Klinikum, Klinikum der Ludwig Maximilians Universität München, München, Germany.; German Centre for Cardiovascular Research (DZHK), Partner Site Munich, Munich Heart Alliance (MHA), Munich, Germany.; Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands.; Heart Rhythm Management Center, UZ Brussel-VUB, Brussels, Belgium.; Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands.; Department of Cardiovascular Diseases, University Hospitals Leuven, Leuven, Belgium.; Medical Genetics, San Luigi Univesity Hospital, Orbassano, TO, Italy.; Medical Genetics Department, Clinical and Biological Sciences, Univestity of Torino, Orbassano, TO, Italy.; Hospital Trueta, CiberCV, University of Girona, IDIBGI, Girona, Spain.; Cardiovascular Institute, Hospital Clinic, University of Barcelona, Barcelona, Spain.; Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands.; Inherited Cardiac Disease Unit, Cardiology Department, University Hospital Virgen de la Arrixaca, Murcia, Spain.; INSERM, Sorbonne University, UMRS 1166, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France.; Department of Cardiovascular Medicine, Nippon Medical School, Tokyo, Japan.; Department of Bioscience and Genetics, National Cerebral and Cardiovascular Center, Suita, Japan.; Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands.; Université de Nantes, CNRS, INSERM, l'institut du thorax, Nantes, France.