Mount Sinai Researchers Discuss Milestones in Understanding Genetic Variants

Ron Do, PhD, associate professor, Charles Bronfman Institute for Personalized Medicine at Mount Sinai, and Iain Forrest, MD-PhD candidate in Dr Do’s lab, discuss how they hope their recent study findings on penetrance of pathogenic and loss-of-function clinical variants can be used and how genetic data are being used in health care.

Transcript

How do you hope the results of your study will be used?

Do: I'll just say, for this study, we wanted to bring attention to the fact that penetrance appeared variable but generally low and penetrance wasn't necessarily concordant with pathogenicity labels. Penetrance doesn't necessarily mean the same thing as pathogenicity.

Forrest: Adding onto that, we also hope that this study will raise important discussions and dialogue about whether a new type of classification system—one based on penetrance, perhaps—to assess disease risk of variants is warranted and this could actually complement the current system based on pathogenicity, which is a categorical system.

Are we approaching any milestones in the understanding of genetic variants?

Do: We feel that this study is a good first step to understanding the disease risk, or penetrance, of genetic variants. However, more research is needed to calculate penetrance in a much larger number of samples to obtain more accurate penetrance estimates at the variant level.

Forrest: The milestone that we're hitting is that genetic data are being used increasingly inside health care. Improving the precision of our interpretations of variants with penetrance will aid in the integration of an individual's genetic data in their health care and help achieve personalized medicine, whereby an individual's unique sequence of DNA can actually shape their clinical care.