Purpose of review: To discuss implications of information garnered through whole-genome and exome sequencing in the practice of cardiovascular medicine.
Recent findings: Whole-genome and exome sequencing unveils medical information embedded in individual genomes and exomes, which could be incorporated into the practice of medicine for diagnostic and therapeutic gains. The human, however, has considerable genetic diversity, as each genome encompasses about 4 million DNA sequence variants (DSVs). The challenging task is to identify the variants that have clinical implications. DSVs exert a continuum of effect sizes on the phenotype that ranges from negligible to large. From a clinical perspective, selected categories, in order of their significance, are disease-causing, likely disease-causing, disease-associated, biologically functional but unknown clinical significance, and unknown functional and clinical significance variants. The frequency of DSVs in the genome also follows a gradient from rare for the disease-causing variants to common for variants with unknown clinical and biological significance. A subset of DSVs might have implications in accurate and preclinical diagnosis, prognostication and individualization of therapy. Clinical phenotypes, however, are too complex to be determined solely by a single DSV. Even in the case of disease-causing variants, the severity of the disease is determined by multiple additional genetic and nongenetic factors.
Summary: Medical DNA sequencing is expected to retool clinicians with the information content of DSVs. DSVs with large effect sizes are likely to offer clinical utility in early and preclinical diagnosis, prognostication and individualization of therapy.