J wave syndrome-susceptibility mutations versus benign rare variants: How do we decide?

Jamie D. Kapplinger, David J. Tester, Michael J. Ackerman

Research output: Chapter in Book/Report/Conference proceedingChapter


Over the past 20 years, the genetic underpinnings of J Wave Syndrome have expanded from the sentinel gene, SCN5A, to over 20 disease-susceptibility genes. Counter to the expansion of our understanding of the potential genetic basis underlying this disorder, our ability to confidently interpret the clinical significance of variants in these disease-susceptibility genes is desperately wanting. This is largely due to the drastic underestimation of the level of genetic variation in these genes as recently identified by large sequencing projects utilizing next generation sequencing technology. This “background rate” of benign genetic variation has led to an interpretive dilemma for the physician: How do we decide whether my patient’s variant is his/her pathogenic mutation or just a benign, rare one? Throughout this chapter, we walk through the current lines of evidence that can be utilized to further enhance the interpretation of rare variants in the J Wave Syndrome diseasesusceptibility genes.

Original languageEnglish (US)
Title of host publicationJ Wave Syndromes
Subtitle of host publicationBrugada and Early Repolarization Syndromes
PublisherSpringer International Publishing
Number of pages30
ISBN (Electronic)9783319315782
ISBN (Print)9783319315768
StatePublished - Jan 1 2016


  • Arrhythmias
  • Brugada syndrome
  • Early repolarization syndrome
  • Genetic testing
  • Genetics
  • J wave syndrome
  • Mutation
  • Polymorphism

ASJC Scopus subject areas

  • General Medicine
  • General Biochemistry, Genetics and Molecular Biology


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