Managing Variant Interpretation Discrepancies in Hereditary Cancer: Clinical Practice, Concerns, and Desired Resources

  • Ellen Zirkelbach
  • Syed Hashmi
  • Aarti Ramdaney
  • Leslie Dunnington
  • Myla Ashfaq
  • Elizabeth K. Nugent
  • Kate Wilson
Original Research

Abstract

Variant interpretation is a complex process, and classification may vary between sources. This study aimed to determine the practice of cancer genetic counselors regarding discrepancies in variant interpretation and to identify concerns when counseling these discrepancies. An electronic survey was sent to genetic counselors in the NSGC Cancer Special Interest Group. The vast majority of counselors (93%) had seen a variant interpretation discrepancy in practice. A large majority (96%) of respondents indicated that they conducted their own research on reported variants. Most respondents cited variant databases as the most common resource utilized in researching variants. Approximately 33% of counselors spent 45 min or more of extra time researching a discrepancy compared to researching a variant with a single classification. When asked how they approached counseling sessions involving variant interpretation discrepancies, the free responses emphasized that counselors considered family history, clinical information, and psychosocial concerns, showing that genetic counselors tailored the session to each individual. Discrepancies in variant interpretation are an ongoing concern for clinical cancer genetic counselors, as demonstrated by the fact that counselors desired further resources to aid in addressing these discrepancies, including a centralized database (89%), guidelines from a major organization (88%), continuing education about the issue (74%), and functional studies (58%). Additionally, most respondents reported that the ideal database would be owned by a non-profit organization (59%) and obtain information directly from laboratories (91%). This investigation was the first to address these discrepancies from a clinical point of view. The study demonstrates that discrepancies in variant interpretation are a concern for clinical cancer genetic counselors and outlines the need for additional support.

Keywords

Variant Discrepancy Cancer Concerns Resources Clinic Database Functional studies Interpretation 

Notes

Acknowledgements

This research was performed in partial fulfillment of the requirements for the MS degree from The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences; The University of Texas Health Science Center at Houston, Texas 77030.

Compliance with Ethical Standards

All research protocols met the requirements of the University of Texas Health Committee for the Protection of Human Subjects, and this study was assigned approval number HSC-MS-16-0436.

Conflicts of Interest

Ellen Zirkelbach, Syed Hashmi, Aarti Ramdaney, Leslie Dunnington, Myla Ashfaq, and Elizabeth K. Nugent declare no conflicts of interest. Kate Wilson is employed by Quest Diagnostics.

Human Studies and Informed Consent

No human studies were carried out by the authors for this article.

Animal Studies

No animal studies were carried out by the authors for this article.

Ethics

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study.

Supplementary material

10897_2017_184_MOESM1_ESM.docx (28 kb)
ESM 1 (DOCX 28 kb)

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Copyright information

© National Society of Genetic Counselors, Inc. 2017

Authors and Affiliations

  • Ellen Zirkelbach
    • 1
    • 2
  • Syed Hashmi
    • 3
  • Aarti Ramdaney
    • 1
  • Leslie Dunnington
    • 4
  • Myla Ashfaq
    • 4
  • Elizabeth K. Nugent
    • 5
  • Kate Wilson
    • 6
  1. 1.Department of Obstetrics, Gynecology, and Reproductive Sciences, Genetic Counseling Program, UTHealth Graduate School of Biomedical SciencesThe University of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Los AngelesUSA
  3. 3.Department of Pediatrics, Pediatric Research Center, UTHealth Graduate School of Biomedical SciencesThe University of Texas MD Anderson Cancer CenterHoustonUSA
  4. 4.Department of Pediatrics, Division of Medical Genetics, UTHealth Graduate School of Biomedical SciencesThe University of Texas MD Anderson Cancer CenterHoustonUSA
  5. 5.Department of Obstetrics, Gynecology, and Reproductive Sciences, Division of Gynecologic Oncology, UTHealth Graduate School of Biomedical SciencesThe University of Texas MD Anderson Cancer CenterHoustonUSA
  6. 6.Medical Affairs, Quest Diagnostics LaboratoryAtlantaUSA

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