Real-World Evaluation of a Population Germline Genetic Screening Initiative for Family Medicine Patients

Megan Leigh Hutchcraft, Shulin Zhang, Nan Lin, Ginny Lee Gottschalk, James W. Keck, Elizabeth A. Belcher, Catherine Sears, Chi Wang, Kun Liu, Lauren E. Dietz, Justine C. Pickarski, Sainan Wei, Roberto Cardarelli, Robert S. DiPaola, Jill M. Kolesar

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Hereditary factors contribute to disease development and drug pharmacokinetics. The risk of hereditary disease development can be attenuated or eliminated by early screening or risk reducing interventions. The purpose of this study was to assess the clinical utility of germline medical exome sequencing in patients recruited from a family medicine clinic and compare the mutation frequency of hereditary predisposition genes to established general population frequencies. At the University of Kentucky, 205 family medicine patients underwent sequencing in a Clinical Laboratory Improvement Amendments of 1988-compliant laboratory to identify clinically actionable genomic findings. The study identified pathogenic or likely pathogenic genetic variants—classified according to the American College of Medical Genetics and Genomics variant classification guidelines—and actionable pharmacogenomic variants, as defined by the Clinical Pharmacogenetics Implementation Consortium. Test results for patients with pharmacogenomic variants and pathogenic or likely pathogenic variants were returned to the participant and enrolling physician. Hereditary disease predisposition gene mutations in APOB, BRCA2, MUTYH, CACNA1S, DSC2, KCNQ1, LDLR, SCN5A, or SDHB were identified in 6.3% (13/205) of the patients. Nine of 13 (69.2%) underwent subsequent clinical interventions. Pharmacogenomic variants were identified in 76.1% (156/205) of patients and included 4.9% (10/205) who were prescribed a medication that had pharmacogenomic implications. Family physicians changed medications for 1.5% (3/205) of patients to prevent toxicity. In this pilot study, we found that with systemic support, germline genetic screening initiatives were feasible and clinically beneficial in a primary care setting.

Original languageEnglish
Article number1297
JournalJournal of Personalized Medicine
Issue number8
StatePublished - Aug 2022

Bibliographical note

Funding Information:
This research was funded by the National Cancer Institute at the National Institutes of Health which provided support for the Biostatistics and Bioinformatics Shared Resource Facility, the Oncogenomics Shared Resource Facility, and the Cancer Research Informatics Shared Resource Facilities of the University of Kentucky Markey Cancer Center (grant number P30CA177558, B. Mark Evers) and the College of Medicine Dean’s Office. We acknowledge Donna Gilbreath for help with figure development.

Publisher Copyright:
© 2022 by the authors.


  • family medicine
  • genetic screening
  • pharmacogenomics
  • real-world

ASJC Scopus subject areas

  • Medicine (miscellaneous)


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