Interpretation and actionability of genetic variants in cardiomyopathies: a position statement from the European Society of Cardiology Council on cardiovascular genomics

Author:

Arbustini Eloisa1ORCID,Behr Elijah R.2ORCID,Carrier Lucie34ORCID,van Duijn Cornelia5ORCID,Evans Paul6,Favalli Valentina7,van der Harst Pim8ORCID,Haugaa Kristina Hermann910ORCID,Jondeau Guillaume111213ORCID,Kääb Stefan1415,Kaski Juan Pablo1617ORCID,Kavousi Maryam18,Loeys Bart1920ORCID,Pantazis Antonis21,Pinto Yigal22,Schunkert Heribert2324,Di Toro Alessandro1ORCID,Thum Thomas2526ORCID,Urtis Mario1ORCID,Waltenberger Johannes2728ORCID,Elliott Perry2930ORCID

Affiliation:

1. Transplant Research Area and Centre for Inherited Cardiovascular Diseases, Department of Medical Sciences and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

2. Cardiology Research Section and Cardiovascular Clinical Academic Group, Institute of Molecular and Clinical Sciences, St George’s, University of London and St George’s University Hospitals NHS Foundation Trust, London, UK

3. Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

4. DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany

5. Nuffield Department of Population Health, University of Oxford, Oxford, UK

6. Department of Infection, Immunity and Cardiovascular Disease, and INSIGNEO Institute, University of Sheffield, Sheffield S10 2RX, UK

7. Genetics and Bioinformatics, 4bases SA, Lugano, CH, Switzerland

8. Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands

9. ProCardio Center for Innovation, Department of Cardiology, Oslo University Hospital, Rikshospitalet, Postboks 4950 Nydalen, Oslo 0424, Norway

10. University of Oslo, Boks 1072 Blindern, Oslo 0316, Norway

11. CNMR Syndrome de Marfan et apparentés, Member of VASCERN, AP-HP Hopital Bichat, Service de Cardiologie, 46 rue Henri Huchard, Paris 75018, France

12. INSERM LVTS U1148, Paris 75018, France

13. Université de Paris, Paris, France

14. Medizinische Klinik und Poliklinik I, LMU University Hospital Munich, Munich, Germany

15. German Center for Cardiovascular Research, Munich Heart Alliance, Munich, Germany

16. Institute of Cardiovascular Science, University College London, London, UK

17. Centre for Inherited Cardiovascular Diseases, Great Ormond Street Hospital, London, UK

18. Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

19. Cardiogenomics, Center for Medical Genetics, Antwerp University Hospital/University of Antwerp, Antwerp, Belgium

20. Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands

21. The Royal Brompton and Harefield Hospitals, Part of Guy’s and St Thomas’ NHS Foundation Trust, London, UK

22. Department of Experimental Cardiology, University of Amsterdam, Amsterdam University Medical Center, Meibergdreef 15, Amsterdam 1105 AZ, The Netherlands

23. Department of Cardiology, Deutsches Herzzentrum München, Technische Universität München, München, Germany

24. Deutsches Zentrum für Herz- und Kreislaufforschung (DZHK), Munich Heart Alliance, Munich, Germany

25. Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Hannover, Germany

26. Fraunhofer Institute of Toxicology and Experimental Medicine (ITEM), Hannover, Germany

27. Department of Cardiology and Cardiovascular Medicine, Medical Faculty, University of Münster, Münster, Germany

28. Cardiovascular Medicine, Hirslanden Klinik Im Park, Seestrasse 220, Zürich 8027, Switzerland

29. Barts Heart Centre St Bartholomew’s Hospital, London, UK

30. Institute for Cardiovascular Science, University College London, London, UK

Abstract

Abstract This document describes the contribution of clinical criteria to the interpretation of genetic variants using heritable Mendelian cardiomyopathies as an example. The aim is to assist cardiologists in defining the clinical contribution to a genetic diagnosis and the interpretation of molecular genetic reports. The identification of a genetic variant of unknown or uncertain significance is a limitation of genetic testing, but current guidelines for the interpretation of genetic variants include essential contributions from clinical family screening that can establish a de novo assignment of the variant or its segregation with the phenotype in the family. A partnership between clinicians and patients helps to solve major uncertainties and provides reliable and clinically actionable information.

Publisher

Oxford University Press (OUP)

Subject

Cardiology and Cardiovascular Medicine

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