Broad sharing of genomic and phenotypic data is needed to inform variant classification, gene-disease validity assessments, and genomic medicine. The Clinical Genome Resource (ClinGen) has engaged 2340 patients in data sharing through its patient registry, GenomeConnect, since 2014. The registry is open to anyone who has had genetic testing, and, to date, has shared 969 sequence variants with ClinVar. These efforts have resulted in 491 (51%) previously unsubmitted sequence variants being added to ClinVar, additional case-level evidence being made available, 25 variant classification updates being identified and shared, and numerous requests for additional information from clinicians and researchers. Given GenomeConnect’s success in patient data sharing, we sought to broaden efforts by working with external registries that may be collecting data but not sharing publicly. We initiated a pilot to engage patient registries in data sharing and assess the utility of data shared from these groups. Here, we report on a pilot of 100 individuals from five external registries in the Patient-Data Sharing Program. From July 2018 and May 2019, five organizations began engaging participants in data sharing – Association for Creatine Deficiencies, Cardio-Facio-Cutaneous Syndrome International, CureCADASIL, No Stomach For Cancer, and GM1 Gangliosidosis. Registry participants control their participation via an online consent within their registries. Those who opt to share data are asked to upload a copy of their genetic testing report to their account to allow for uniform data mining, may be invited to complete additional surveys to collect additional phenotype data, and are provided with the option to receive updates regarding their results. Fifty-six percent of participants uploaded their report. Genetic counselors reviewed reports to ensure standardized data collection and submitted de-identified data to ClinVar. A total of 81 unique variants were shared, of which 45.6% (n=37/81) were novel to ClinVar demonstrating that condition specific registries are a source of novel variants. Participants also provided additional health and case-level information that could inform future gene and variant curation efforts, such as those performed by ClinGen. Of variants that were previously submitted by the reporting laboratory, 12% (n=3/25) were out of date compared to the current classification. These pilot data show that registries can empower patients to contribute valuable information to the public knowledge base, benefiting patients and the genetics community.
