Identification and triage of patients with incidental germline pathogenic variants on somatic tumor profiling with a genomics module

Abstract

When cancer patients undergo tumor profile testing with paired tumor tissue and germline samples, incidental germline pathogenic variants are identified in up to 1 of 8 cases. Genetic counselors (GCs) play an important role in identifying these patients for genetic counseling referral and confirmatory germline testing. Tumor profile tests are typically ordered by medical oncologists, so a collaborative partnership with GCs supports appropriate follow-up. Manual methods to identify these patients can be time-consuming and tedious. In 2020, our team implemented a genomics module in the electronic health record system (EHR) and completed integration with the tumor testing laboratory. We used discrete variants in our EHR to create a reporting workbench tool to identify patients with incidental germline pathogenic variants. A protocol for triaging flagged patients to traditional vs. embedded care confirmatory germline testing was developed for appropriate referral. Patients were considered eligible for GC referral and confirmatory germline testing after excluding those who were deceased, previously tested, or declined confirmatory germline testing with documentation in the EHR. From 2020 to 2024, the GC referral rate increased from 27% to 100% and the confirmatory germline testing rate increased from 27% to 66%. Of all incidental germline pathogenic variants that underwent confirmatory germline testing, 100% were confirmed. Confirmatory germline testing did reveal secondary pathogenic variants not reported initially on tumor profile tests. We found additional pathogenic variants in 8.6% (2/23) and 9.7% (3/31) of patients tested in 2023 and 2024, respectively. Between 2019 and 2024, 192 total incidental germline patients were identified. The proportion of patients who underwent tumor profile testing with incidental germline findings was 7.3% overall, which is concordant with previously reported study rates. Discrete identification of potential germline variants via EHR integration supported the efficient triaging of patients eligible for GC referral and confirmatory germline testing, contributing to a 100% referral rate in 2024. Integration of the testing laboratory creates opportunity for further EHR application, such as Best Practice Alerts and Health Maintenance Care Gaps. Building laboratory integration for discrete genomic variants increases reporting capabilities, patient tracking, cascade testing, and could be applied to many broader medical contexts.