“It turns out mutations are the norm. You expect to find mutations in a gene. It’s a very different way of thinking about the human genome. If you don’t find a mutation, your machine is probably having technical difficulty,” Resta says.

When scientists test for mutations in large numbers of genes with a single test, known as a gene panel, they are virtually guaranteed to find at least one VUS, says Colleen Caleshu, a genetic counsellor at Stanford University’s Center for Inherited Cardiovascular Disease. “The more genes you look at, the more variation you’ll find,” she adds. “We all have tons of variations in our genes, most of which are extremely rare and, by the very nature of rarity, uninterpretable.” In short, there isn’t enough data to know what you are seeing.

Catherine Losing / Mosaic

This gray area has only expanded as next-generation DNA sequencing has led to the growing use of gene panels, to look for mutations in a range of genes that may be related to a patient’s symptoms. Of the three possible results—pathogenic, benign, or unknown—pathogenic is the least common, says Resta. You’re much more likely to get uncertainty.

If interpreting genetic testing results is difficult for clinicians, it’s also tremendously hard for patients. Yvonne Bombard has spent the last several years of her career as a genomics health services researcher at St. Michael’s Hospital in Toronto, working to understand how families make sense of genetic testing results.

“There’s very little research on the impact of uncertain results on families yet—the technology is just too new,” Bombard says.

A small study in Psycho-Oncology surveyed 24 women with breast or ovarian cancer who had received VUS results for their genetic testing. Many of them had a distorted perception of what those results meant. Although two-thirds correctly remembered three years later that the variants detected by the test were unclassified, 79 percent interpreted the results as a higher genetic risk for developing cancer. One-third had also made significant medical changes in their lives based only on their test results, which Resta and Caleshu do not recommend.

Families of children with suspected genetic diseases have similar difficulties. Parents tend to interpret any variant that’s not classified “benign” as being the cause of their child’s disease, explains Caleshu. But she appreciates how it’s hard not to do that, especially when families have been looking for answers for so long.

Families can feel let down by the medical establishment, who often seem to throw up their hands when a patient defies diagnosis, and in the absence of definitive answers it’s all too easy to believe that the genetic variants identified on the test must be what’s wrong. One of Caleshu’s main jobs is providing pre-test counseling so that patients understand the risks and the limitations of testing. She says her team has changed the way they present results, so that patients and doctors don’t read too much into a VUS. Even with the right genetic counseling, however, uncertainty can be agonizing.

Ciccarella had watched her mother endure chemotherapy, and had undergone a similar grueling regimen herself. If she could get genetic information that might help her children and any future generations to avoid that agony by using improved screening, reproductive planning, and prophylactic mastectomies, then she was determined to make that happen.

She decided to get another lab to review the results of her genetic tests, and requested the data from the sequencing company, Myriad Genetics. They refused. Since they owned patents on these genes, no one else could have their proprietary genetic data.