From Genotype to Phenotype.

Genomic variants associated with inherited cardiac conditions yet detected incidentally (‘secondary findings’) are likely to arise with increasing frequency as genome sequencing transitions into clinical practice. Since genotyping has until recently been directed by clinical diagnosis, assessment and management of individuals found to harbour such a variant as a secondary finding is unclear. Here we illustrate some diagnostic and psychosocial complexities of inherited cardiac condition secondary findings, exemplified by disclosure of a pathogenic variant in KCNQ1, associated with long QT syndrome, to a healthy male enrolled in diagnostic genome sequencing as an unaffected relative. This early case represents a shift from ‘phenotype-to-genotype’ to ‘genotype-to-phenotype’; we describe clinical evaluation, family history and a qualitative research interview with the secondary finding recipient, discuss the role of specialist services in variant interpretation, genetic counselling and clinical assessment, and some challenges of realising improved health outcomes following disclosure of a secondary finding.