Exome Sequencing Reanalysis: Past practices and patient characteristics at a single institution

Abstract We performed a cross-sectional, retrospective review of our institution's previous uninformative exome sequencing (ES) results and reanalysis process, and we identified areas of improvement in our genetic testing pipeline. To accomplish this, we performed a detailed chart review of patients who had ES performed from 2013 through 2016 and catalogued data including age, indication for testing, ordering physician specialty, and if a reanalysis was performed. Our final sample included 165 patients with uninformative exome sequencing results, 50 of whom also had reanalysis. Then, descriptive statistics and Fishers exact tests were performed to identify factors associated with whether ES reanalysis had been completed or not. We found that certain factors were more closely associated with a patient having had a reanalysis performed for a normal or uninformative result, like whether the patient had a future appointment within our institution (p = 0.0276). Other factors more closely associated with a patient having reanalysis were if the patient met with a geneticist (p = 0.0018) and/or genetic counselor (p = 0.0027). Other variable such as age, race, and if the patient had a future appointment with their ordering provider were not associated with an increased likelihood of having reanalysis. These results highlight the value of genetics professionals in interpreting complex genetic testing and also identify areas where we may need to improve our current processes. In addition, our results confirm findings from previous studies, implement a basis for other clinics to examine their ES reanalyses pipeline, and allow us to support the call for additional guidelines on ES reanalysis.