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Comment & Response
June 14, 2016

Long QT Syndrome and Potentially Pathogenic Genetic Variants

Author Affiliations
  • 1National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland
JAMA. 2016;315(22):2467. doi:10.1001/jama.2016.2918

To the Editor Dr Van Driest and colleagues1 presented a negative study on novel criteria for secondary variants for long QT syndrome. They identified 127 candidate SCN5A or KCNH2 variants and considered 63 potentially pathogenic, using unspecified review criteria in 3 clinical laboratories. This number reflects an overall rate of 3.1%, which, as they noted, is unexpectedly high and biologically implausible, because the upper estimate of long QT syndrome prevalence is 1 in 2500 (or minor allele frequency [MAF] of 0.02%). As expected, by using such liberal criteria, they found that these variants were not associated with an abnormal phenotype.

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