Variant Assessment for Reduced Penetrance Diseases

Heritable disorders can often be linked back to a specific gene or genetic variant which transmits the risk of disease across generations. In most cases, the penetrance, or risk of being affected by the disease, for a pathogenic variant carrier is less than 100%. For an increasing number of disorders, the penetrance is even lower (20-50%), which begins to confound our ability to understand the relationship between disease risk and a specific genetic variant. At this level, classical tools, including family and functional studies, for assessment of variant pathogenicity loose power. This webinar will address the utility of the different lines of evidence in the classification of variants in moderate penetrance disease and recommended modifications to multivariate analysis in this setting.