A goal of the 3rd phase of the Electronic Medical Records and Genomics (eMERGE3) Network was to examine the return of results (RoR) of actionable variants in more than 100 genes to consenting participants and their healthcare providers. Each of the 10 eMERGE sites developed plans for three essential elements of the RoR process: Disclosure to the participant, notification of the health care provider, and integration of results into the electronic health record (EHR). Procedures and protocols around these three elements were adapted as appropriate to individual site requirements and limitations. Detailed information about the RoR procedures at each site was obtained through structured telephone interviews and follow-up surveys with the clinical investigator leading or participating in the RoR process at each eMERGE3 institution. Because RoR processes at each of the 10 sites allowed for taking into account differences in population, disease focus and institutional requirements, significant heterogeneity of process was identified, including variability in the order in which patients and clinicians were notified and results were placed in the EHR. This heterogeneity in the process flow for eMERGE3 RoR reflects the “real world” of genomic medicine in which RoR procedures must be shaped by the needs of the patients and institutional environments.

A challenge in returning genomic test results to research participants is how best to communicate complex and clinically nuanced findings to participants in a manner that is scalable to the large numbers of participants enrolled. The purpose of this study was to examine the features of genetic results letters produced at each Electronic Medical Records and Genomics (eMERGE3) Network site to assess their readability and content. Letters were collected from each site, and a qualitative analysis of letter content and a quantitative analysis of readability statistics were performed. Because letters were produced independently at each eMERGE site, significant heterogeneity in readability and content was found. The content of letters varied widely from a baseline of notifying participants that results existed to more detailed information about positive or negative results, as well as materials for sharing with family members. Most letters were significantly above the Centers for Disease Control-suggested reading level for health communication. While continued effort should be applied to make letters easier to understand, the ongoing challenge of explaining complex genomic information, the implications of negative test results, and the uncertainty that comes with some types of test and result makes simplifying letter text challenging.

Purpose: The electronic Medical Records and Genomics (eMERGE) Phase III study was undertaken to assess clinical utility of returning medically actionable genomic screening results. We assessed pediatric clinical outcomes following return of pathogenic/likely pathogenic (P/LP) variants in autosomal dominant conditions with available effective interventions. Methods: The two eMERGE III pediatric sites collected outcome data and assessed changes in medical management at 6 and 12 months. Results: We returned P/LP results to 29 participants with outcome data. For 23 of the 29 participants, the P/LP results were previously unknown. Five of the 23 participants were already followed for conditions related to the P/LP variant. Of those receiving novel results and not being followed for the condition related to the P/LP result (n = 18), 14 (77.8%) had a change in healthcare after return of results (RoR). Following RoR, cascade testing of family members occurred for 10 of 23 (43.5%). Conclusions: The most common outcomes post-RoR included imaging/laboratory testing and health behavior recommendations. A change in healthcare was documented in 77.8% of those receiving results by 6 months. Our findings demonstrate how return of genomic screening results impacts healthcare in pediatric populations.

Importance: Approximately 10% of cancers are attributable to heritable germline variants, yet identification of individuals at risk remains suboptimal. Objective: To assess the feasibility of personal history and family health history (FHH) risk assessment technology via the electronic medical record (EMR) to enhance identification of patients at risk for a broad array of inherited cancer syndromes. Design, Setting, and Participants: This single-arm, nonrandomized clinical trial was completed from October 1, 2021, to September 1, 2023, with no follow-up period in unselected patients receiving care at Vanderbilt University Medical Center. Adult patients (aged ≥18 years) were invited through their EMR patient portals to complete an eligibility survey. Eligible participants completed the survey, were English speaking, and had no prior genetic counseling. The data analysis was performed between August 15 and November 7, 2025. Intervention: Electronic medical record–integrated risk assessment platform that collected self-reported personal history and FHH to assess risk for 24 hereditary cancer syndromes. Main Outcomes and Measures: The primary outcome was the completion rate of the risk assessment platform. Secondary outcomes included the percentage of newly identified participants meeting guideline criteria for genetic counseling and whether previsit FHH collection increased genetic counseling capacity by decreasing time spent in counseling. Results: A total of 1685 patients were consented to participate (mean [SD] age, 55.4 [15.1] years; 1217 female [72.2%]; 95 of Black or African American [5.6%] 1405 of White [83.4%], and 181 of other [multiracial, other, or unknown] [10.6%] race; 38 of Hispanic or Latino [2.3%], 1388 of non-Hispanic or Latino [82.4%], and 111 of unknown [6.6%] ethnicity). Among participants consented, 1483 (88.0%) were provided access to the risk assessment, 1106 (74.6%) started the assessment, 636 (57.5%) completed it, and 544 (49.1%) received a risk report. Younger age and unknown race and ethnicity were the only significant variables associated with completion (mean [SD] age, 53.5 [15.3] vs 56.9 [14.8] years for completers vs noncompleters, respectively; unknown race, 77 [14.2%] vs 43 [7.6%] for noncompleters; unknown ethnicity, 49 [9.0%] vs 20 [3.6%] for completers vs noncompleters, respectively). Among participants who completed the risk assessment, 155 (28.5%) met guideline criteria for genetic counseling, yet 74 (47.7%) were previously identified as at risk by billing codes. A total of 31 participants (20.0%) eligible for genetic counseling attended. Manual outreach efforts and counseling duration did not differ between risk assessment–assisted and usual care visits. Conclusions and Relevance: In this nonrandomized clinical trial, almost one-third of the population met national genetic counseling criteria for an inherited cancer syndrome, highlighting a substantial gap in usual care identification. Integrating patient-facing FHH collection and assessment tools for primary care patients improves inherited cancer risk identification and highlights opportunities to further enhance both risk assessment processes and genetic counseling attendance. Trial Registration: ClinicalTrials.gov Identifier: NCT05079334