Table 1.

The optimistic and negative attitudes from the literature are extracted and organized by indication in Table 1. (Studies where the participants were asked about what they thought about VUSs, but they did not have a VUS result, are defined as “hypothetical”)

Indication	Positive affective response to VUS themes	Negative affective response to VUS themes
Undiagnosed disease 3 articles, Combined N = 77	• Potential answers in the future • Optimism • Contributing to research • Empowerment • Gratitude	• Disappointment at not receiving a diagnosis • Distress over uncertainty • Frustration • Disappointment
Prenatal /chromosome array parents 4 articles, Combined N = 64 1 hypothetical article, N = 147	• Relief • Comfort • Happiness • Validation • Acceptance • Extra information • Preparedness	• Hopelessness • Guilt • Isolation • Feeling of permanence • Distress from uncertainty • Lack of answers
Cardiomyopathy 3 articles Combined, N = 93	• Contributing to research • Contributing to future knowledge • Useful information • Sense of self awareness	• Dissatisfaction from uncertainty • Decisional regret of learning about their result • Lack of understanding and recall
Fabry-associated c.427G > A (p.A143T) variant in GLA 1 article, N = 27	• Ability to plan for the future • Inform clinical care	• Frustrated by lack of clear information • Decisional regret of learning about their result
Lynch syndrome 1 article, N = 27 1 hypothetical article, N = 19	• Relief • Empowerment • Hope • Viewed not as definitive diagnosis, therefore better than a positive test result	• Sadness • Conflict • Disappointment • Shocking • Decisional regret
Breast cancer (of the articles reviewed) 5 articles combined N = 246 1 hypothetical article, N = 60	• Viewed not as definitive, therefore better than a positive test result • Potential answers in the future	• Frustration about uncertainty • Isolation • Disappointment • Distress • Greater sustained distress
Tumor 1 article n = 11 2 Combined hypothetical, N = 458	• Participation in research • Hope for the future	• Distress • Uncertainty • Worry about increased medical costs • Confusion
Research participants 1 article, N = 26 2 hypothetical articles combined, N = 241	• Optimism that it would be reclassified • Opportunity • Furthering scientific knowledge	• Uncertainty • Pessimism • Fear • Distrust • Misunderstanding