Mutations in theSCN5A gene, which encodes the cardiac sodium channel, are well known to cause gain or loss of channel function and, consequently, various cardiac arrhythmias. However, greater phenotypic variability exists than can be ascribed directly to mutation-dependent changes in channel biophysical properties. In this Perspectives article, Liu et al. propose that additional intrinsic and extrinsic modifiers of channel behaviour might help to explain this variability and to improve genotype–phenotype correlations.
- Man Liu
- Kai-Chien Yang
- Samuel C. Dudley Jr
