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.