title: Clinical whole-exome sequencing: are we there yet?
abstract: BACKGROUND
  Clinical laboratories began offering whole-exome sequencing in 2011 at a cost between $4,500 and $9,000. Reported detection rates for deleterious mutations range from 25 to 50%. Based on the experience of our clinical genetics service, actual success rates may be lower than estimated rates. We report results from our own experience along with a survey of clinical geneticists to ascertain (i) current success rates for causal gene detection in a clinical setting; (ii) if there are insurance authorization issues; and (iii) if turnaround times quoted by the clinical laboratories are accurate; we also gauge provider opinions toward clinical whole-exome sequencing.
  
  
  METHODS
  We reviewed our results and the results of a survey that was electronically distributed to 47 clinical genetics centers.
  
  
  RESULTS
  A total of 35 exome reports were available. If all positive results are collated, we observe a success rate of 22.8%. One result incorrectly identified a known benign variant as pathogenic. Some insurers covered all testing, whereas others denied any insurance coverage. Only three (23.1%) of our reports were available within the laboratory's quoted turnaround times. More than 50% of clinicians queried in our survey had not ordered whole-exome sequencing at the current time, many stating concerns regarding interpretation, insurance coverage, and cost.
  
  
  CONCLUSIONS
  Clinical whole-exome sequencing has proven diagnostic utility; however, currently many clinicians have concerns regarding interpretation of results, insurance coverage, and cost.
authors: Division of Medical Genetics, Stanford University Medical Center, Stanford, California, USA.
authors: Paldeep Singh
authors: PS
authors: Atwal
authors: Division of Medical Genetics, Stanford University Medical Center, Stanford, California, USA.
authors: Marie-Louise
authors: ML
authors: Brennan
authors: Division of Medical Genetics, Stanford University Medical Center, Stanford, California, USA.
authors: Rachel
authors: R
authors: Cox
authors: Division of Medical Genetics, Stanford University Medical Center, Stanford, California, USA.
authors: Michael
authors: M
authors: Niaki
authors: Division of Medical Genetics, Stanford University Medical Center, Stanford, California, USA.
authors: Julia
authors: J
authors: Platt
authors: Division of Medical Genetics, Stanford University Medical Center, Stanford, California, USA.
authors: Margaret
authors: M
authors: Homeyer
authors: Division of Medical Genetics, Stanford University Medical Center, Stanford, California, USA.
authors: Andrea
authors: A
authors: Kwan
authors: Division of Medical Genetics, Stanford University Medical Center, Stanford, California, USA.
authors: Sylvie
authors: S
authors: Parkin
authors: Division of Medical Genetics, Stanford University Medical Center, Stanford, California, USA.
authors: Susan
authors: S
authors: Schelley
authors: Division of Medical Genetics, Stanford University Medical Center, Stanford, California, USA.
authors: Leah
authors: L
authors: Slattery
authors: Division of Medical Genetics, Stanford University Medical Center, Stanford, California, USA.
authors: Yael
authors: Y
authors: Wilnai
authors: Division of Medical Genetics, Stanford University Medical Center, Stanford, California, USA.
authors: Jonathan Adam
authors: JA
authors: Bernstein
authors: Division of Medical Genetics, Stanford University Medical Center, Stanford, California, USA.
authors: Gregory M
authors: GM
authors: Enns
authors: Division of Medical Genetics, Stanford University Medical Center, Stanford, California, USA.
authors: Louanne
authors: L
authors: Hudgins
mesh_terms: D059472:Exome; D030342:Genetic Diseases, Inborn / Q000175:diagnosis / Q000235:genetics; D005820:Genetic Testing; D019538:Health Care Surveys; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans