How do we determine the significance of genetic variants?

Research Program

We want to be able to accurately predict the phenotype of any and all genetic variants. Our approach is to collect as much phenotype information--at high and low resolution--as is feasible for the largest number of variants and then leverage high-throughput experimental and computational methods to fill in the details for yet uncharacterized variants. To develop this methodology, we are starting with ion channels involved in the heart contraction cycle. See this talk on YouTube for an overview to our research program.

What is our progress to date?

Publications

Above is a video highlighting an intersection of protein structure and clinical presentation, in this case for the sodium ion channel Nav1.5 (gene SCN5A). Variants associated with Brugada syndrome (BrS1, blue), type 3 long QT syndrome (LQT3, red), or unaffected carriers (gold) are shown as spheres. This representation suggests the utility of using structure and residue annotation to understand mechanism and generate predictions about yet uncharacterized variants found in structured regions.

What can help you determine the significance of genetic variants?

Resources

A list of useful resources for those trying to determine the significance of genetic variants.

Who does this work?

People

Current and past group members