Progress in science is a continuum but not uniform. Occasional sparks, typically ignited by the so-called disruptive discoveries, decorate the continuum. Relevant to this editorial on advances in the genetic testing technologies, is the disruptive technology of capillary sequencing, also known as Sanger sequencing.1 It enabled the initial sequencing of the human genome2,3 and led to the second Noble prize for the late Dr Fred Sanger in 1980 (http://www.nobelprize.org/nobel_prizes/chemistry/laureates/1980/). The simple and elegant capillary sequencing technology ushered in the dawning of the most successful years in cardiovascular genetics and deciphering the genetic basis of single gene cardiovascular disorders, such as hereditary cardiomyopathies, ion channel disorders, and autosomal-dominant hypercholesterolemia, among others.4–8 The advances also enabled genetic testing based on the candidate gene approach, albeit the approach was time consuming, labor intensive, and relatively expensive. Hence, genetic testing based on the Sanger sequencing technique did not make the transition from the research laboratories to the bedside. Nevertheless, the genetic discoveries based on Sanger sequencing had an enormous impact on genetics as well as in medicine. This is exemplified by discovery of PCSK9 as a causal gene for autosomal-dominant hypercholesterolemia in 2003.5 The pace of subsequent mechanistic discoveries and advances toward the clinical applications were blazingly fast. 9 Within a decade of the discovery of the gene, its function was partially unraveled, and monoclonal antibodies to inhibit PCSK9 were developed, and shown to be clinically effective in lowering low-density lipoprotein cholesterol and improving clinical outcomes.10,11 Subsequently, Food and Drug Administration recently approved 2 PCSK9 inhibitors for clinical use in a subset of patients with high low-density lipoprotein cholesterol. Article, see p 603 The elegant Sanger sequencing technique, however, was no exception to unrelenting technological advances, and soon it was all but replaced …