How people undergoing genomic sequencing interpret and react to varied secondary findings with limited actionability

To investigate patient reactions to and understanding of secondary genomic findings with limited to no medical actionability (LMA-SFs) from diagnostic genome sequencing. We analyzed LMA-SFs returned to 47 adults who elected to receive a broad set of these results from 6 categories. Findings indicated elevated risk (reportable/positive) or not (negative/normal). Most participants (<i>N</i> = 43) also completed surveys to report their distress, decision regret, expected health anxiety, and whether and how they perceived results as reassuring or troubling. Most participants received some reportable LMA-SFs for common risk, pharmacogenetic, and carrier status variants. Fewer received reportable <i>APOE</i> haplotype or monogenetic condition variants. None received results indicating high risk for severe neurological disease. Overall, participants (76.7% female, 97.7% White) had low distress, decision regret, and expected health anxiety. None described negative/normal findings as troubling. However, their interpretations of reportable/positive results varied. Even within the same result type, some participants found them troubling, while others found them reassuring based on their perception of the results’ utility. Participants’ short-term well-being was not reduced by receiving LMA-SFs. Their interpretations suggested varied personal utilities and the need for post-test resources to aid understanding of these types of results and their health significance. Genomic sequencing can find a diagnosis for people who have symptoms that suggest they may have a hereditary disease. It can also find results that do not change medical treatment for most people. This study looks at whether people feel distressed when they get secondary findings that will give them little to no medically useful information. Because these findings can be hard to understand, we also asked people to explain what their findings meant to them. We found that learning these findings did not make people feel distressed. Also, people who received the same or similar results felt differently about the results they received. Some felt their results were good news, while others were worried. Even when they learned about higher health risk, some people felt it was useful because it helps them plan. In sum, we found NO/LITTLE evidence that secondary findings caused distress in patients. We should learn more about how personal understanding influences future health decisions.