Identifying individuals with medically actionable, hereditary syndromes such as Lynch Syndrome (LS) can lead to reduced morbidity and mortality. However, prior evaluations of LS screening programs in the endometrial cancer context find that the biggest threat to their success, by orders of magnitude, is the high rate of non- consent for sequencing. Largely due to non-consent, protocols that call for sequencing following immunohistochemistry (IHC)?positive screens are estimated to miss 58% of LS index cases, while direct-to- sequencing screening protocols are expected to miss 30%. It is not known, however, why non-consent occurs: perhaps people misunderstand some important aspect of genetic sequencing, or perhaps they have concerns (e.g., genetic privacy) that could be better or more thoroughly addressed during the consent process. Traditional, in-person consent for sequencing faces two additional challenges: reaching patients in rural and other medically underserved areas and ensuring that screening protocols are cost-effective. Electronic consent (eConsent) shows promise in overcoming barriers of both access and cost and has begun to be used in important genomics projects, including the All of Us Research Program, yet has never been rigorously compared to traditional consent to ensure non-inferiority. Working with Sage Bionetworks, we adapted the eConsent framework they developed for All of Us to Geisinger's MyCode Community Health Initiative, which involves population screening for clinically actionable variants, including LS. We propose a pragmatic, non- inferiority RCT?which we have already piloted?of Sage eConsent compared to traditional consent. In addition to determining whether eConsent is non-inferior in ensuring patient comprehension (Aim 1), this study will help identify aspects of genomic screening that are difficult for patients to understand or that they express a preference to learn more about, which will inform both eConsent and traditional consent processes, and potentially improve screening uptake (Aim 2). Compared to conducting this study in a LS-only screening population, the large MyCode population will provide sufficient sample size to power a non-inferiority trial over a short period of time. Moreover, as the cost of sequencing continues to decline, population genomic screening will itself become a viable, cost-effective approach to identifying individuals with LS and other hereditary syndromes. Indeed, multiple health systems are already piloting such programs, which will require scalable, accessible, and cost-effective approaches to consent. The results of this study will greatly benefit the IMPULSS implementation toolkit that will be designed to help institutions implement, evaluate, and adapt LS screening programs over time, particularly as it becomes cost-effective for institutions to move their programs towards a direct-to-sequencing protocol in cancer patients or to population screening. Including data on the costs and effectiveness of scalable eConsent for sequencing will be a valuable addition to the IMPULSS toolkit that can help reduce barriers to identifying individuals with hereditary cancer risk in order to prevent cancer.