Novel findings with reassessment of exome data: implications for validation testing and interpretation of genomic data.

Kristin McDonald Gibson, Addie Nesbitt, Kajia Cao, Zhenming Yu, Elizabeth Denenberg, Elizabeth DeChene, Qiaoning Guan, Elizabeth Bhoj, Xiangdong Zhou, Bo Zhang, Chao Wu, Holly Dubbs, Alisha Wilkens, Livija Medne, Emma Bedoukian, Peter S White, Jeffrey Pennington, Minjie Lou, Laura Conlin, Dimitri Monos, Mahdi Sarmady, Eric Marsh, Elaine Zackai, Nancy Spinner, Ian Krantz, Matt Deardorff, Avni Santani,

Genetics in medicine : official journal of the American College of Medical Genetics, November 30, -0001

The objective of this study was to assess the ability of our laboratory’s exome-sequencing test to detect known and novel sequence variants and identify the critical factors influencing the interpretation of a clinical exome test.MethodsWe developed a two-tiered validation strategy: (i) a method-based approach that assessed the ability of our exome test to detect known variants using a reference HapMap sample, and (ii) an interpretation-based approach that assessed our relative ability to identify and interpret disease-causing variants, by analyzing and comparing the results of 19 randomly selected patients previously tested by external laboratories. We demonstrate that this approach is reproducible with >99% analytical sensitivity and specificity for single-nucleotide variants and indels

Pubmed Link: 29389922

DOI: 10.1038/gim.2017.153