Classification of Genetic Variants

  • Maurizio Genuardi
  • Elke Holinski-Feder
  • Andreas Laner
  • Alexandra Martins


Widespread resequencing for research and diagnostic purposes has disclosed a huge amount of genetic variability in the human genome, including the genes associated with inherited predisposition to colorectal cancer. The functional and clinical consequences of the gene variants identified are often difficult to predict. Therefore, it has becoming increasingly evident that standardized approaches for the clinical interpretation of gene variants are needed in order to maximize the clinical utility of molecular testing. In this chapter, we discuss strategies for variant classification, with special reference to hereditary colorectal cancer genes and to the functional and clinical points of evidence that are available for their interpretation.


mRNA functional studies Alternative splicing Nonsense- mediated mRNA decay In vitro protein assays In silico prediction tools Multifactorial Bayesian analysis Variants of uncertain significance (VUS) 


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Maurizio Genuardi
    • 1
    • 2
  • Elke Holinski-Feder
    • 3
    • 4
  • Andreas Laner
    • 3
  • Alexandra Martins
    • 5
  1. 1.Institute of Genomic Medicine, Catholic University of the Sacred HeartRomeItaly
  2. 2.Fondazione Policlinico Universitario “A. Gemelli”RomeItaly
  3. 3.Medizinische Klinik und Poliklinik IV, Campus Innenstadt, Klinikum der Universität MünchenMunichGermany
  4. 4.MGZ – Medizinisch Genetisches ZentrumMunichGermany
  5. 5.Inserm-U1245-IRIB, Normandy Centre for Genomic and Personalized Medicine, University of RouenRouenFrance

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