2013 NSGC: Disease Diagnosis by Exome Sequencing: Issues Hampering Causative Variant Discovery

Exome sequencing is increasingly utilized in clinical genetics practice to diagnose cases where other genetic testing has proven futile or cost-inefficient. However, the limitations of next-generation sequencing technologies, particularly with respect to commonly utilized “off-the-shelf” exome enrichments, result in poor coverage of certain disease-causing mutations. Several issues also exist in variant identification and annotation.