The Return of Actionable Variants Empirical (RAVE) Study, a Mayo Clinic Genomic Medicine Implementation Study: Design and Initial Results.

TitleThe Return of Actionable Variants Empirical (RAVE) Study, a Mayo Clinic Genomic Medicine Implementation Study: Design and Initial Results.
Publication TypeJournal Article
Year of Publication2018
AuthorsKullo, IJ, Olson, J, Fan, X, Jose, M, Safarova, M, Breitkopf, CRadecki, Winkler, E, Kochan, DC, Snipes, S, Pacyna, JE, Carney, M, Chute, CG, Gupta, J, Jose, S, Venner, E, Murugan, M, Jiang, Y, Zordok, M, Farwati, M, Philogene, M, Smith, E, Shaibi, GQ, Caraballo, P, Freimuth, R, Lindor, NM, Sharp, R, Thibodeau, SN
JournalMayo Clin Proc
Date Published2018 Nov
KeywordsCardiovascular Diseases, Cohort Studies, Colon, Female, Genetic Predisposition to Disease, Genetic Testing, Genomics, Humans, Hyperlipidemias, Male, Middle Aged, Outcome Assessment, Health Care, Phenotype, Polymorphism, Single Nucleotide, Polyps, Surveys and Questionnaires

OBJECTIVES: To identify clinically actionable genetic variants from targeted sequencing of 68 disease-related genes, estimate their penetrance, and assess the impact of disclosing results to participants and providers.

PATIENTS AND METHODS: The Return of Actionable Variants Empirical (RAVE) Study investigates outcomes following the return of pathogenic/likely pathogenic (P/LP) variants in 68 disease-related genes. The study was initiated in December 2016 and is ongoing. Targeted sequencing was performed in 2533 individuals with hyperlipidemia or colon polyps. The electronic health records (EHRs) of participants carrying P/LP variants in 36 cardiovascular disease (CVD) genes were manually reviewed to ascertain the presence of relevant traits. Clinical outcomes, health care utilization, family communication, and ethical and psychosocial implications of disclosure of genomic results are being assessed by surveys, telephone interviews, and EHR review.

RESULTS: Of 29,208 variants in the 68 genes, 1915 were rare (frequency

CONCLUSION: Expected traits were present in 13% of participants with P/LP variants in non-FH CVD genes, suggesting low penetrance; this estimate may change with additional testing performed as part of the clinical evaluation. Ongoing analyses of the RAVE Study will inform best practices for genomic medicine.

Alternate JournalMayo Clin Proc
PubMed ID30392543
PubMed Central IDPMC6652203
Grant ListK24 HL137010 / HL / NHLBI NIH HHS / United States
R01 HL135879 / HL / NHLBI NIH HHS / United States
U01 HG006379 / HG / NHGRI NIH HHS / United States

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