2014 NSGC: A Negative Result on Exome Sequencing: What a Genetic Counselor Should Know

Exome sequencing is increasingly utilized in the diagnosis of disorders of unknown genetic etiology. Despite increasing evidence for the utility of this approach, the majority of patients presenting with a presumed Mendelian genetic trait receive a negative sequencing report. Both technical and biological factors contribute to the current difficulty in deriving diagnoses from genomic sequence information, and genetic counselors ordering exome sequencing tests should be aware of the following issues.