O23: Genotype-first analysis of individuals in the All of Us Research Program with pathogenic variation causal for three highly penetrant conditions

The FACToR Scale assesses negative impact of results, with higher scores indicating greater impact.Negatives (M= 16.8, SD= 12.9) reported less impact than positives (M= 34.0, SD= 20.0) (p=<.001), and Group 1 (M= 29.4,SD= 16.8) less than Group 2 (M= 53.6, SD= 20.8) (p=<.001).Most parents interviewed recalled easy decision-making about enrollment.Primary motivations were information seeking and ease of participation.Key concerns were fear of a positive result, worry due to past testing, and data privacy.Parents suggested increasing prenatal awareness and information about genes tested.Some had not understood that follow-up testing may be required.Most felt the unscheduled results call was effective while some suggested a scheduled phone/video call.Resources accessed included the internet, family groups, and scientific literature.Feedback was positive regarding the utility of diagnoses with accessible and potentially life-saving management.Most said their needs were met somewhat or completely by GUARDIAN and recommended others consider enrolling.Conclusion: Early experiences with GUARDIAN underscore the importance of adaptability and collaboration.Partnerships with the New York State Department of Health, pediatricians and subspecialists are essential to the study's early successes.Feedback from families is invaluable to the study's evolution.Future studies will include assessments of medical impact.