A 14-year-old in heart failure with multiple cardiomyopathy variants illustrates a role for signal-to-noise analysis in gene test re-interpretation.

Variants of unknown significance in cardiomyopathic disease should be analyzed systematically based on the prevalence of the variant in the population compared to prevalence of disease, evidence that other variants in the gene are pathologic, consistency of prediction software on pathogenicity, and the current clinical consensus.