With current NGS platforms, the boundaries of variant detection and gene content for genetic disease panels has been vastly expanded leading to increases in detection rates. However these platforms also bring different technical and interpretive challenges faced by molecular diagnostic laboratories. Using hearing loss genetic testing as an example, strategies to overcome these challenges will be explored with an emphasis on alleviating the genetic data interpretation burden and improving assay performance. These approaches can lead to faster turnaround times and lower the cost of testing, while lessening the ambiguities of clinical genetic reports. Learning Objectives: 1. Describe technical challenges of targeted gene panel sequencing, such as CNV analysis and pseudogene contamination, and potential solutions that clinical laboratories can implement to retain analytical sensitivity and specificity. 2. Assess clinical panel inclusion for genes using on an evidence based approach, with examples from genes associated with nonsyndromic hearing loss.