Distinguishing Hypertrophic CardiomyopathyAssocia

Authors: Jamie D Kapplinger Andrew P Landstrom J Martijn Bos Benjamin A Salisbury Thomas E Callis Michael J Ackerman

Publish Date: 2014/02/08

Volume: 7, Issue: 3, Pages: 347-361

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Abstract

Despite the significant progress that has been made in identifying diseaseassociated mutations the utility of the hypertrophic cardiomyopathy HCM genetic test is limited by a lack of understanding of the background genetic variation inherent to these sarcomeric genes in seemingly healthy subjects This study represents the first comprehensive analysis of genetic variation in 427 ostensibly healthy individuals for the HCM genetic test using the “gold standard” Sanger sequencing method validating the background rate identified in the publically available exomes While mutations are clearly overrepresented in disease a background rate as high as ∼5  among healthy individuals prevents diagnostic certainty To this end we have identified a number of estimated predictive valuebased associations including genespecific topology and conservation methods generating an algorithm aiding in the probabilistic interpretation of an HCM genetic test

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