Interpreting Incidentally Identified Variants in Genes Associated With Heritable Cardiovascular Disease: A Scientific Statement From the American Heart Association

Circ Genom Precis Med. 2023 Apr;16(2):e000092. doi: 10.1161/HCG.0000000000000092. Epub 2023 Mar 27.

Abstract

Rapid advances in genetic technologies have led to expanding use of diagnostic, research, and direct-to-consumer exome and genome sequencing. Incidentally identified variants from this sequencing represent a significant and growing challenge to interpret and translate into clinical care and include variants in genes associated with heritable cardiovascular disease such as cardiac ion channelopathies, cardiomyopathies, thoracic aortic disease, dyslipidemias, and congenital/structural heart disease. These variants need to be properly reported, the risk of associated disease accurately assessed, and clinical management implemented to prevent or lessen the disease so that cardiovascular genomic medicine can become both predictive and preventive. The goal of this American Heart Association consensus statement is to provide guidance to clinicians who are called on to evaluate patients with incidentally identified genetic variants in monogenic cardiovascular disease genes and to assist them in the interpretation and clinical application of variants. This scientific statement outlines a framework through which clinicians can assess the pathogenicity of an incidental variant, which includes a clinical evaluation of the patient and the patient's family and re-evaluation of the genetic variant in question. Furthermore, this guidance underscores the importance of a multidisciplinary team to address these challenging clinical evaluations and highlights how clinicians can effectively interface with specialty centers.

Keywords: AHA Scientific Statements; aortic diseases; cardiomyopathies; cardiovascular diseases; channelopathies; dyslipidemias; genomics; patient care team.

Publication types

  • Review

MeSH terms

  • American Heart Association
  • Cardiovascular Diseases* / genetics
  • Genetic Counseling
  • Genetic Predisposition to Disease*
  • Genetic Variation
  • Humans
  • United States