Clinical DNA Variant Interpretation

Clinical DNA Variant Interpretation

Theory and Practice

1st Edition - February 27, 2021

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  • Editor: George Patrinos
  • eBook ISBN: 9780128205204
  • Paperback ISBN: 9780128205198

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Clinical DNA Variant Interpretation: Theory and Practice, a new volume in the Translational and Applied Genomics series, covers foundational aspects, modes of analysis, technology, disease and disorder specific case studies, and clinical integration. This book provides a deep theoretical background, as well as applied case studies and methodology, enabling researchers, clinicians and healthcare providers to effectively classify DNA variants associated with disease and patient phenotypes. Practical chapters discuss genomic variant interpretation, terminology and nomenclature, international consensus guidelines, population allele frequency, functional evidence transcripts for RNA, proteins, and enzymes, somatic mutations, somatic profiling, and much more.

Key Features

  • Compiles best practices, methods and sound evidence for DNA variant classification in one applied volume
  • Features chapter contributions from international leaders in the field
  • Includes practical examples of variant classification for common and rare disorders, and across clinical phenotypes


Active researchers, basic and translational scientists, and clinicians in the areas of human genetics, genomics, reproductive medicine, gynecology, obstetrics, internal medicine, oncology, psychiatry, neurology,  immunology, embryology, endocrinology, bioinformatics, prenatal testing, psychology, psychiatry, and genetic testing; genetic counselors; bioethicists; fertility specialists; hospital administrators

Table of Contents

  • 1. Introduction: The challenge of genomic DNA interpretation

    Section I. Theoretical Chapters
    2. General considerations: Terminology and standards
    3. International consensus guidelines for constitutional sequence variant interpretation
    4. Quantitative modelling: Multifactorial integration of data
    5. Clinical and genetic evidence and population evidence
    6. The computational approach to variant interpretation: principles, results, and applicability
    7. Functional evidence (I) transcripts and RNA splicing outline
    8. Functional evidence (II) protein and enzyme function
    9. Somatic data usage for classification of germline variants
    10. Pharmacogenomics and personalized medicine
    11. Data sharing and gene variant databases
    12. Approaches to the comprehensive interpretation of genome-scale sequencing
    13. Phenotype evaluation and clinical context: Application of case-level data in genomic variant interpretation

    Section II. Practical Chapters
    14. Inherited cardiomyopathies
    15. Phenylketonuria
    16. Hearing loss
    17. Familial hypercholesterolemia
    18. Classification of genetic variants in hereditary cancer genes
    19. RASopathies
    20. Summary and conclusions


Product details

  • No. of pages: 436
  • Language: English
  • Copyright: © Academic Press 2021
  • Published: February 27, 2021
  • Imprint: Academic Press
  • eBook ISBN: 9780128205204
  • Paperback ISBN: 9780128205198

About the Series Editor

George Patrinos

George Patrinos is Professor of Pharmacogenomics at the University of Patras School of Health Sciences (Department of Pharmacy) in Patras, Greece with Adjunct positions in Rotterdam, the Netherlands and Al-Ain, United Arab Emirates. His research interests span the fields of pharmacogenomics and personalised medicine, focused on psychiatric diseases and hemoglobinopathies, the implementation of genomics into healthcare, particularly for health systems in developing countries, the development of genomic databases and web-based translational tools for personalised medicine and the application of genomics in public health. George Patrinos has published more than 270 scientific papers in peer reviewed journals on topics related to genetics, genomic medicine, pharmacogenomics, molecular diagnostics, and social and economic evaluation for genomic medicine. He is also the editor of several textbooks published by Elsevier/Academic Press, including the renowned textbook "Molecular Diagnostics", published by Elsevier now in its third edition. He serves as Editor-In-Chief and Communicating and Associate Editor for several high impact scientific journals and he is co-organizer of the international meeting series “Golden Helix Conferences”.

Affiliations and Expertise

Professor, Department of Pharmacy, University of Patras School of Health Sciences, Patras, Greece; United Arab Emirates University, College of Medicine and Health Sciences, Department of Pathology, Al-Ain, UAE, United Arab Emirates University, Zayed Center of Health Sciences, Al-Ain, UAE and Erasmus University Medical Center, School of Medicine and Health Sciences, Department of Pathology – Bioinformatics Unit, Rotterdam, The Netherlands

About the Editors

Conxi Lázaro

Conxi Lázaro PhD, is Head of the Molecular Diagnostic Laboratory, Hereditary Cancer Program, Catalan Institute of Oncology-IDIBELL-CIBERONC at Hospitalet de Llobregat, Barcelona, Spain. Dr Lazaro is a molecular geneticist with more than 25 years of experience in the field of human genetics. She did her PhD in Human Genetics at University of Barcelona. She has worked in several clinical hospitals in Barcelona. She was an invited professor at Massachusetts General Hospital Cancer Center at Boston in 2003/04 and did a sabbatical stay at Mount Sinai Hospital and at Women's College Hospital in Toronto in 2018/19. In the last ten years she has been involved in several projects aimed at using Next Generation Sequencing (NGS) for genetic testing purposes. Her field of expertise is Hereditary Cancer although she has worked on other genetic disorders. Of relevance was her pivotal research in the genetic basis of Neurofibromatosis type 1 (NF1) since the gene was discovered and her current work on the development of new therapeutic strategies for malignant tumors associated with NF1. She is member of several reputable international consortia and associations such as CIMBA, ENIGMA, CTF, GENTURIS and had been member of the Scientific Program Committee of the ESHG as well as treasurer of the Spanish association of human genetics (ASHG).

Affiliations and Expertise

Head of the Molecular Diagnostic Unit, Hereditary Cancer Program, Barcelona, Spain

Jordan Lerner-Ellis

Dr. Jordan Lerner-Ellis has 20 years of experience in molecular genetics and diagnostics. He is Director & Head of Advanced Molecular Diagnostics in the department of Pathology and Laboratory Medicine at Toronto’s Mount Sinai Hospital, Sinai Health System; Associate Professor at the University of Toronto, Laboratory Medicine & Pathobiology; and Clinician Scientist at the Lunenfeld-Tanenbaum Research Institute. His laboratory provides clinical diagnostic services for hereditary breast, ovarian and colon cancer, and other genetic testing areas, for Toronto and the province of Ontario. Dr Lerner-Ellis completed his PhD in human genetics at McGill University. He continued his studies at the Children’s Hospital in Basel, Switzerland before moving on to a postdoctoral fellowship in Molecular Biology at Harvard University, the Massachusetts General Hospital, and in Medical and Population Genetics at the Broad Institute. Following his postdoctoral studies, Dr. Lerner-Ellis completed the Clinical Molecular Genetics training program at Harvard Medical School, Brigham and Women’s Hospital and is certified as a diplomate of the American Board of Medical Genetics. Dr Lerner-Ellis’ core interest is in molecular diagnostics as currently applied to breast and colon cancer. His research is focused on improving genetic testing through greater reliance on new sequencing technologies. A concurrent aim of his research is to integrate genome sequencing into the general practice of medicine. Dr Lerner-Ellis is active in national and international data sharing, and variant interpretation efforts aimed at improving our understanding of the relationship between DNA variants and disease.

Affiliations and Expertise

Associate Professor, Laboratory Medicine & Pathobiology, University of Toronto; Director & Head of Advanced Molecular Diagnostics, Pathology & Laboratory Medicine, Mount Sinai Hospital, Sinai Health, Toronto, Ontario, Canada.

Amanda Spurdle

Amanda Spurdle is an Associate Professor and Group Leader in Molecular Cancer Epidemiology at QIMR Berghofer Medical Research Institute, Australia. She co-founded and currently leads the ENIGMA international research consortium ( aimed at improving and applying methods to determine the clinical significance of sequence variants in breast-ovarian cancer susceptibility genes. She is active in multiple expert panels dealing with interpretation of variants in cancer susceptibility genes.

Affiliations and Expertise

Associate Professor and Group Leader, Molecular Cancer Epidemiology, QIMR Berghofer Medical Research Institute, Australia

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