Distinguishing hypertrophic cardiomyopathy-associated mutations from background genetic noise.

Kapplinger, JD

Landstrom, AP

Bos, JM

Salisbury, BA

Callis, TE

Ackerman, MJ

2020-04-01T13:37:54Z

2020-04-01T13:37:54Z

2014-04

2020-04-01T13:37:54Z

Despite the significant progress that has been made in identifying disease-associated 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 value-based associations including gene-specific, topology, and conservation methods generating an algorithm aiding in the probabilistic interpretation of an HCM genetic test.

1937-5387

1937-5395

https://hdl.handle.net/10161/20316

eng

Springer Science and Business Media LLC

Journal of cardiovascular translational research

10.1007/s12265-014-9542-z

Sarcomeres

Humans

Cardiomyopathy, Hypertrophic

Sequence Analysis, DNA

Genomics

Polymorphism, Genetic

Adolescent

Adult

Middle Aged

Female

Male

Young Adult

Genetic Testing

Distinguishing hypertrophic cardiomyopathy-associated mutations from background genetic noise.

Journal article

Landstrom, AP|0000-0002-1878-9631

347

361

3

School of Medicine

Cell Biology

Pediatrics, Cardiology

Duke

Basic Science Departments

Pediatrics

Clinical Science Departments

Published

7