Is it time to reassess variant annotation?

Variant annotation is one of the most essential steps in selecting candidates for further investigation. With the advancement in functional genomics, new variant annotation tools focus on annotation based on empirically generated data instead of theoretically based predictions. This is a direct result of the large national and international consortia that generated enormous experiment-based or validated data at multiple omics levels. Here, we highlight the recent empirically based annotation methods and discuss their strengths and weaknesses.