The Probability of Pathogenicity in Clinical Genetic Testing: A Solution for the Variant of Uncertain Significance


  •  Michael Gollob    
  •  Jeffrey S. Rosenthal    
  •  Kevin Thorpe    

Abstract

We present a direct calculation for determining the probability that a rare genetic variant is the cause of an observed disease, under appropriate assumptions, in terms of the joint prevalence of the disease and of rare variants.  Our calculation provides a resolution of the so-called ``variant of unknown (or uncertain) significance'' problem, which has plagued medical genetics researchers.


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