An analysis of medical records has revealed patients with genetic variations presumed to cause cardiac disorders often did not have any symptoms or signs of a heart condition. According to the authors of the new study, their results call into question the validity of "actionable" findings in prior genetic reports.

The American College of Medical Genetics and Genomics (ACMG) has generated a list of genetic variants that are known to be, or in some cases predicted to be, detrimental to a patient's future health. On this basis, the authors of the study explain, the ACMG recommends these irregularities be disclosed to patients anytime they are discovered in genomic sequencing data. With the sequencing of exomes and genomes increasingly used in clinical practice, both the relevance and disclosure of rare variants is now taking on greater importance — especially since it is unclear how frequently a variant will manifest as disease.

Which findings are actionable?

For the current study, researchers at Vanderbilt University Medical Center reviewed data from electronic medical records to assess the clinical relevance of rare variants. In particular, they focused on patients possessing genetic variations in arrhythmia susceptibility genes; SCN5A and KCNH2 have both been designated pathogenic. Looking for these two genetic variations, the team's analysis included medical records from 2,022 patients recruited from seven academic centers in the United States between 2002 and 2014. Among the 2,022 participants in the Electronic Medical Records and Genomics Network Pharmacogenomics project, a total of 122 rare variants were identified in 223 individuals (11 percent of the study cohort).

Comparing participants with variants to those without, the researchers found no difference in prevalence of arrhythmia diagnoses as recorded in their medical records. In fact, little more than a third (35 percent) of participants with genetic variants showed any evidence of arrhythmia, the researchers said.

How can this poor showing be explained? According to the researchers, some participants may have signs of disease not yet documented in their medical records. Or, without additional genetic or environmental influences, these variants may only cause subclinical disease, they suppose.

No matter how the results are explained, the new study exposes "shortcomings in the existing ability to meaningfully predict the consequences of at least some genetic variations currently thought to be causally related to serious disorders," wrote Dr. William Gregory Feero, Maine Dartmouth Family Medicine Residency, in an editorial. He suggests caution be exercised "when considering clinical interventions informed by the presence of 'pathogenic' variations in healthy individuals, families, and populations."

Whether it's national security or your health, deciding what is "actionable" and what is not makes all the difference in the world.

Source: Van Driest SL, Wells QS, Stallings S, et al. Association of Arrhythmia-Related Genetic Variants With Phenotypes Documented in Electronic Medical Records. JAMA. 2016.