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Should variants of unknown significance (VUS) be disclosed to patients in cardiogenetics or not; only in case of high suspicion of pathogenicity?

European Journal of Human Genetics volume 30, pages 1208–1210 (2022)Cite this article

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In an adult/pediatric patient with a suspected inherited cardiac disease, genetic testing to clarify the clinical condition is nowadays part of standard routine clinical care. Apart from identifying a likely pathogenic (LP, class 4) or pathogenic (P, class 5) variant, test results can also be confusing when a variant of unknown significance (VUS, class 3) is identified. In cardiogenetics this happens in ~35–40% of patients [1]. In our experiences in Sweden and the Netherlands, it can be hard for both healthcare professionals and patients to distinguish the difference between a VUS and a (L)P variant, sometimes leading to communication difficulties regarding the possibility of genetic testing in the family. During a recent ERN exchange between our centers it became obvious that we handle the dissemination of VUS-es to the patient differently, where Umeå, Sweden,  has a more restrictive policy.

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Fig. 1: Current and proposed strategy for dealing with VUS-es in cardiogenetics.

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This paper did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Clinical Genetics, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands

    Saskia N. van der Crabben & Hennie Bikker

  2. European Reference Network for rare, low-prevalence, or complex diseases of the heart (ERN GUARD-Heart), Amsterdam, the Netherlands

    Saskia N. van der Crabben, Stellan Mörner, Anna C. Lundström, Jenni Jonasson, Hennie Bikker, Ahmad S. Amin, Annika Rydberg & Arthur A. M. Wilde

  3. Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

    Stellan Mörner

  4. Department of Clinical Science, Umeå University, Umeå, Sweden

    Anna C. Lundström & Annika Rydberg

  5. Department of Medical Biosciences, Mecial and Clinical Genetics, Umeå University, Umeå, Sweden

    Jenni Jonasson

  6. Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences Amsterdam University Medical Centers, University of Amsterdam, Heart Center, Amsterdam, the Netherlands

    Ahmad S. Amin & Arthur A. M. Wilde

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  1. Saskia N. van der Crabben
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  8. Arthur A. M. Wilde
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Contributions

SvdC and AAMW designed and wrote the manuscript; SM, ACL, JJ, HB, ASA, AR were essential for the discussion on the topic of VUS-es and provided feedback on the manuscript.

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Correspondence to Saskia N. van der Crabben.

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van der Crabben, S.N., Mörner, S., Lundström, A.C. et al. Should variants of unknown significance (VUS) be disclosed to patients in cardiogenetics or not; only in case of high suspicion of pathogenicity?. Eur J Hum Genet 30, 1208–1210 (2022). https://doi.org/10.1038/s41431-022-01173-z

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  • DOI: https://doi.org/10.1038/s41431-022-01173-z

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