Frontiers in Genetics (Jul 2015)
How well do whole exome sequencing results correlate with medical findings? A study of 89 Mayo Clinic Biobank samples
Abstract
Whole Exome Sequencing (WES) is increasingly being used for diagnosis without adequate information on predictive characteristics of reportable variants typically found on any given individual and correlation with clinical phenotype. In this study, we performed WES on 89 deceased individuals (mean age at death 74 years, range 28-93) from the Mayo Clinic Biobank. Significant clinical diagnoses were abstracted from electronic-medical-record via chart review. Variants (Single Nucleotide Variant and insertion/deletion) were filtered based on quality (accuracy >99%, read-depth >20, alternate-allele read-depth >5, minor-allele-frequency 0.19). Evaluating genotype-phenotype correlations across the exome, 202 (3%) of 7046 filtered variants had some evidence for phenotypic correlation in medical-records, while 3710 (53%) variants had no phenotypic correlation. The phenotype associated with the remaining 44% could not be assessed from a typical medical record review. These data highlight significant continued challenges in the ability to extract medically meaningful predictive results from WES.
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