Variants of Uncertain Significance and Communities of Practice in Clinical Genomics

• In Event: Innovation, Biocapital and the Making of Post-Genomic Medicine - I

Abstract

This paper explores a key challenge raised by the clinical implementation of genomic technologies (such as Array CGH, Whole exome sequencing) which is the way in which they generate large numbers of variants of uncertain (or unknown) significance (VUSs), sections of DNA the value of which – benign, neutral or pathogenic - is unknown at time of testing.
Unlike the ‘known unknowns’ of risk decisions, VUSs present professionals with a number of dilemmas: how should such variants be classified (there are a number of schemes available in the literature) and how strong does new evidence need to be to shift a variant to a new classification (for example, ‘benign’ to ‘probably pathogenic’); given the evidence of patients’ confusion and potential distress associated with VUS results (in part because their uncertainty is in contrast to the probabilistic nature of most genetic results) how is this information communicated to patients.
This paper presents data from a comparative ethnography of clinical decision making, looking at the ways in which specialists from a range of different disease areas (cancer, inherited heart disease, developmental disorders) deal with these issues, exploring the factors that lead to the development of different ‘communities of practice’.

Author

• Adam Hedgecoe, Cardiff University