Let’s say that you have a family history of breast cancer. You decide to take a genetic test to assess your risk. But when the results come back, they are, well, indeterminate. You have a genetic variant, but your doctor can’t tell you if it’s harmful or benign.

This frustrating test result is what Lea Starita, Ph.D., UW research assistant professor in genome sciences, calls a variant of uncertain significance.

“A variant could mean that a gene is perfectly normal,” says Starita. “It’s almost like the British version of ‘grey’ versus the American version of ‘gray.’ The word is spelled differently, but it still means the same thing.” In contrast, some alternative spellings — the variants — can lead to cancer and other diseases.

Identifying all these variations, separating harmless from harmful, is a challenge that Starita and others at the Brotman Baty Institute for Precision Medicine (BBI) are taking on. Their aim is to create a huge catalog of genetic variants, including what they do and their response to drugs. Compiling all this data, which will be crucial to making genetic testing effective and relevant, is a big challenge. But it’s a challenge made a little simpler by Starita and Jay Shendure, M.D., Ph.D., scientific director of the BBI.

Alice Berger, Ph.D., an assistant member at Fred Hutchinson Cancer Research Center and part of the variant exploration team, explains. “Jay’s group, together with Lea, have used CRISPR to develop saturation genome editing,” she says. “Rather than studying one mutation at a time — which is how it’s been done for the last 30 years — they’ve figured out how to use a pool of cells to study all possible mutations in the gene at once.”

Speed and capacity are integral to the success of this project. So is the variety of expertise the partners bring to it. Berger, an expert in cancer biology, is deeply interested in lung cancer. Genomicist Starita has been focusing on variants in breast and ovarian cancer. The BBI is bringing them together — along with dozens of their peers at UW Medicine, Fred Hutch and Seattle Children’s — to work on projects, like testing the functions of variants, related to making medicine better and more targeted.

“We’re amassing all of this really amazing data, but we’re not really quite sure how to move it into the clinic,” says Starita. “So we’re really excited about our collaborations with the clinical and medical geneticists and pathologists we’re teaming up with through the BBI. Because that’s their expertise.”

Many scientists, working for the greater good: that’s the BBI.

“I always had this idea that I wanted to be able to see the benefit of my research for humankind in my lifetime,” Berger says. With her partners at the BBI, she thinks she will.

The BBI — a collaboration of UW Medicine, Fred Hutchinson Cancer Research Center and Seattle Children’s — was founded in 2017 by a group of visionary friends: the late Jeffrey H. Brotman and his wife, Susan, and Dan and Pam Baty. Learn more at BrotmanBatyInstitute.org.