Classification is primarily based on clinical actionability, which is divided into 4 categories.

  • Actionable Variants                                                                                         Damaging : An alteration with an effect on proteinfunction (gain, loss or altered) based on several publications by differentresearch groups which include some clinical information
    Probably Damaging : An alteration with an effect on proteinfunction based on only one publication and perhaps only using an in vitromodel and for which no clinical information is available
    Unknown : Analteration with no demonstrated effect on protein function  
  • Variants of Uncertain Significance (VUS)                                                                    An alteration with no demonstratedeffect on protein function 
  • MedicallyActionable Incidental Findings                                                                     An alteration that might be associatedwith a genetic disease or increase susceptibility with some cancer. 
  • Probably Polymorphism                                                                                               An alteration characterized as polymorphism with a minor allele frequency (MAF) ≥1% and not associated with any genetic disease.


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