Journal of Genetic Counseling

, Volume 27, Issue 4, pp 751–760 | Cite as

Clinical Cardiovascular Genetic Counselors Take a Leading Role in Team-based Variant Classification

  • Chloe Reuter
  • Megan E. Grove
  • Kate Orland
  • Katherine Spoonamore
  • Colleen CaleshuEmail author
Original Research


We sought to delineate the genetic test review and interpretation practices of clinical cardiovascular genetic counselors. A one-time anonymous online survey was taken by 46 clinical cardiovascular genetic counselors recruited through the National Society of Genetic Counselors Cardiovascular Special Interest Group. Nearly all (95.7%) gather additional information on variants reported on clinical genetic test reports and most (81.4%) assess the classification of such variants. Clinical cardiovascular genetic counselors typically (81.0%) classify variants in collaboration with cardiologist and/or geneticist colleagues, with the genetic counselor as the team member who is primarily responsible. Variant classification is a relatively recent (mean 3.2 years) addition to practice. Most genetic counselors learned classification skills on the job from clinical and laboratory colleagues. Recent graduates were more likely to have learned this in graduate school (p < 0.001). Genetic counselors are motivated to take responsibility for the classification of variants because of prior experiences with variant reclassification, inconsistencies between laboratories, and incomplete laboratory reports. They are also driven by a sense of professional duty and their proximity to the clinical context. This practice represents a broadening of the skill set of clinical cardiovascular genetic counselors and a unique expertise that they contribute to the interdisciplinary teams in which they work.


Variant classification Cardiovascular Genetic testing Genetic counselor Genetic counseling Interpretation 



We are grateful to the cardiovascular genetic counselors who participated in this study. KS is partially supported by the Indiana University Health – Indiana University School of Medicine Strategic Research Initiative.

Compliance with Ethical Standards

Conflicts of Interest

CR, KO, and MG declare that they have no conflict of interest.

CC has received honoraria for work as an advisor and/or consultant for Phosphorus, Recombine, Invitae, GeneDx, Gilead, Myokardia. She has also received royalties for a patent on genome interpretation technology and holds stock in Personalis.

KS has received honoraria for work as an Advisory Board member for Invitae.

Human Studies and Informed Consent

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.

Animal Studies

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

Supplementary material

10897_2017_175_MOESM1_ESM.docx (29 kb)
ESM 1 (DOCX 29.2 kb)


  1. Ackerman, J. P., Bartos, D. C., Kapplinger, J. D., Tester, D. J., Delisle, B. P., & Ackerman, M. J. (2016). The promise and peril of precision medicine. Mayo Clinic Proceedings, 91(11), 1606–1616. Scholar
  2. Amendola, L. M., Jarvik, G. P., Leo, M. C., McLaughlin, H. M., Akkari, Y., Amaral, M. D., et al. (2016). Performance of ACMG-AMP variant-interpretation guidelines among nine Laboratories in the Clinical Sequencing Exploratory Research Consortium. The American Journal of Human Genetics, 98(6), 1067–1076. Scholar
  3. Andreasen, C., Nielsen, J. B., Refsgaard, L., Holst, A. G., Christensen, A. H., Andreasen, L., et al. (2013). New population-based exome data are questioning the pathogenicity of previously cardiomyopathy-associated genetic variants. European Journal of Human Genetics : EJHG, 21(9), 918–928. Scholar
  4. Aronson, S. J., Clark, E. H., Varugheese, M., Baxter, S., Babb, L. J., & Rehm, H. L. (2012). Communicating new knowledge on previously reported genetic variants. Genetics in Medicine, 14(8), 713–719. Scholar
  5. Arscott, P., Caleshu, C., Kotzer, K., & Kreykes, S. (2016). A case for inclusion of genetic counselors in cardiac care. Cardiology in Review, 24(2), 49–55. Scholar
  6. Balmana, J., Digiovanni, L., Gaddam, P., Walsh, M. F., Joseph, V., Stadler, Z. K., et al. (2016). Conflicting interpretation of genetic variants and cancer risk by commercial laboratories as assessed by the prospective registry of multiplex testing. Journal of Clinical Oncology, 34(34), 4071–4078. Scholar
  7. Bland, A., Dunn, K. E., Pariani, M., Platt, J., Grove, M. E., & Caleshu, C. (2016). Abstract: A single-center experience with clinician interpretation of variants in cardiovascular genetics indicates clinically impactful disagreement with testing laboratories. Journal of Genetic Counseling, 25(6), 1347–1472.CrossRefGoogle Scholar
  8. Caleshu, C., & Ashley, E. A. (2016). Taming the genome : Towards better genetic test interpretation. Genome Medicine, 9–11.
  9. Caleshu, C., Kasparian, N. A., Edwards, K. S., Yeates, L., Semsarian, C., Perez, M., et al. (2016a). Interdisciplinary psychosocial care for families with inherited cardiovascular diseases. Trends in Cardiovascular Medicine, 26(7), 647–653. Scholar
  10. Caleshu, C., Kelly, M., Morales, A., Ashley, E., Hershberger, R., & Funke, B. (2016b). Lack of specificity of ACMG classification rules decreases inter-curator concordance. ClinGen’s adaptation of ACMG’s framework to standardize interpretation of MYH7 related cardiomyopathy variants., (ASHG Annual Meeting). Retrieved from
  11. Das, K. J., Ingles, J., Bagnall, R. D., & Semsarian, C. (2014). Determining pathogenicity of genetic variants in hypertrophic cardiomyopathy: importance of periodic reassessment. Genetics in Medicine, 16(4), 286–293. Scholar
  12. Erskine, K. E., Griffith, E., Degroat, N., Stolerman, M., Silverstein, L. B., Hidayatallah, N., et al. (2013). An interdisciplinary approach to personalized medicine : Case studies from a cardiogenetics clinic P erspective. Personalized Medicine, 10(1), 73–80.CrossRefPubMedPubMedCentralGoogle Scholar
  13. Furqan, A., Arscott, P., Girolami, F., Cirino, A. L., Michels, M., Day, S. M., et al. (2017). Care in Specialized Centers and Data Sharing Increase Agreement in hypertrophic cardiomyopathy genetic test interpretation. Circulation. Cardiovascular Genetics, 10(5), e001700. Scholar
  14. Garber, K. B., Vincent, L. M., Alexander, J. J., Bean, L. J. H., Bale, S., & Hegde, M. (2016). Reassessment of genomic sequence variation to harmonize interpretation for personalized medicine. American Journal of Human Genetics, 99(5), 1140–1149. Scholar
  15. Harrison, S. M., Dolinsky, J. S., Knight Johnson, A. E., Pesaran, T., Azzariti, D. R., Bale, S., et al. (2017). Clinical laboratories collaborate to resolve differences in variant interpretations submitted to ClinVar. American College of Medical Genetics and Genomics: Genet Med Retrieved from Scholar
  16. Hooker, G. W., Ormond, K. E., Sweet, K., & Biesecker, B. B. (2014). Teaching genomic counseling : Preparing the genetic counseling workforce for the genomic era. Journal of Genetic Counseling, 23, 445–451. Scholar
  17. Ingles, J., & Semsarian, C. (2014). Conveying a probabilistic genetic test result to families with an inherited heart disease. Heart Rhythm : The Official Journal of the Heart Rhythm Society, 11(6), 1073–1078. Scholar
  18. Ingles, J., Lind, J. M., Phongsavan, P., & Semsarian, C. (2008). Psychosocial impact of specialized cardiac genetic clinics for hypertrophic cardiomyopathy. Genetics in Medicine : Official Journal of the American College of Medical Genetics, 10(2), 117–120. Scholar
  19. Ingles, J., Yeates, L., & Semsarian, C. (2011). The emerging role of the cardiac genetic counselor. Heart Rhythm : The Official Journal of the Heart Rhythm Society, 8(12), 1958–1962. Scholar
  20. Kelly, M., Caleshu, C., Morales, A., Buchan, J., Wolf, Z., Cook, S., … Funke, B. (in press). Adaptation and Validation of the ACMG/AMP variant classification framework for MYH7-associated inherited cardiomyopathies: Recommendations by ClinGen's Inherited Cardiomyopathy Expert Panel. Genetics in Medicine.Google Scholar
  21. Kurian, A. W., Li, Y., Hamilton, A. S., Ward, K. C., Hawley, S. T., Morrow, M., et al. (2017). Gaps in incorporating Germline genetic testing into treatment decision-making for early-stage breast cancer. Journal of Clinical Oncology, 35(20), 2232–2239. Scholar
  22. Lek, M., Karczewski, K., Minikel, E., Samocha, K., Banks, E., Fennell, T., et al. (2016). Analysis of protein-coding genetic variation in 60,706 humans. Nature, 536(7616), 285–291.CrossRefPubMedPubMedCentralGoogle Scholar
  23. Manrai, A. K., Funke, B. H., Rehm, H. L., Olesen, M. S., Maron, B. A., Szolovits, P., et al. (2016). Genetic misdiagnoses and the potential for health disparities. New England Journal of Medicine, 375(7), 655–665. Scholar
  24. Maron, B. J., Haas, T. S., Doerer, J. J., Thompson, P. D., & Hodges, J. S. (2009). Comparison of U.S. and Italian experiences with sudden cardiac deaths in young competitive athletes and implications for preparticipation screening strategies. The American Journal of Cardiology, 104(2), 276–280. Scholar
  25. Pirzadeh-Miller, S., Robinson, L. S., Read, P., & Ross, T. S. (2017). Genetic counseling assistants: An integral piece of the evolving genetic counseling service delivery model. Journal of Genetic Counseling, 26(4), 716–727. Scholar
  26. Profato, J., Gordon, E. S., Dixon, S., & Kwan, A. (2014). Assessing the integration of genomic medicine in genetic counseling training programs. Journal of Genetic Counseling, 23(4), 679–688. Scholar
  27. Rehm, H. L. (2017). A new era in the interpretation of human genomic variation. Genetics in Medicine, 1–4.
  28. Rehm, H. L., Berg, J. S., Brooks, L. D., Bustamante, C. D., Evans, J. P., Landrum, M. J., et al. (2015). ClinGen — The clinical genome resource. The New England Journal of Medicine, 372(23), 2235–2242.CrossRefPubMedPubMedCentralGoogle Scholar
  29. Richards, S., Aziz, N., Bale, S., Bick, D., Das, S., Gastier-Foster, J., et al. (2015). Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genetics in Medicine, 17(5), 405–423. Scholar
  30. Shah, N., Hou, Y.-C. C., Yu, H.-C., Sainger, R., Dec, E., Perkins, B., … Telenti, A. (2016). Identification of misclassified ClinVar variants using disease population prevalence. bioRxiv. Retrieved from
  31. Spoonamore, K. G., Orland, K., & Caleshu, C. (2016). Abstract: Who are the cardiologists early to adopt integration of genetic counselors into clinical practice? Journal of Genetic Counseling, 25(6), 1347–1472.CrossRefGoogle Scholar
  32. Thompson, B. A., Spurdle, A. B., Plazzer, J.-P., Greenblatt, M. S., Akagi, K., Al-Mulla, F., et al. (2014). Application of a five-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants lodged on the InSiGHT locus-specific database. Nature Genetics, 46(2), 107–115. Scholar
  33. Walsh, R., Thomson, K. L., Ware, J. S., Funke, B. H., Woodley, J., Mcguire, K. J., et al. (2016). Reassessment of Mendelian gene pathogenicity using 7, 855 cardiomyopathy cases and 60, 706 reference samples. Genetics in Medicine, 1–12.
  34. Watkins, H. (2013). Assigning a causal role to genetic variants in hypertrophic cardiomyopathy. Circulation. Cardiovascular Genetics, 6(1), 2–4. Scholar
  35. Yang, S., Lincoln, S. E., Kobayashi, Y., Nykamp, K., Nussbaum, R. L., & Topper, S. (2017). Sources of discordance among germ-line variant classifications in ClinVar, 1–9.

Copyright information

© National Society of Genetic Counselors, Inc. 2017

Authors and Affiliations

  • Chloe Reuter
    • 1
  • Megan E. Grove
    • 2
    • 3
  • Kate Orland
    • 4
  • Katherine Spoonamore
    • 5
  • Colleen Caleshu
    • 1
    • 2
    Email author
  1. 1.Stanford Center for Inherited Cardiovascular DiseaseStanford UniversityStanfordUSA
  2. 2.Clinical Genomics ServiceStanford Health CareStanfordUSA
  3. 3.Division of Medical GeneticsStanford UniversityStanfordUSA
  4. 4.Division of Cardiovascular Medicine, School of Medicine and Public HealthUniversity of Wisconsin-MadisonMadisonUSA
  5. 5.Krannert Institute of Cardiology, Department of MedicineIndiana University School of MedicineIndianapolisUSA

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