Atwal Paldeep Singh, Brennan Marie-Louise, Cox Rachel, Niaki Michael, Platt Julia, Homeyer Margaret, Kwan Andrea, Parkin Sylvie, Schelley Susan, Slattery Leah, Wilnai Yael, Bernstein Jonathan Adam, Enns Gregory M, Hudgins Louanne
Division of Medical Genetics, Stanford University Medical Center, Stanford, California, USA.
Genet Med. 2014 Sep;16(9):717-9. doi: 10.1038/gim.2014.10. Epub 2014 Feb 13.
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.
We reviewed our results and the results of a survey that was electronically distributed to 47 clinical genetics centers.
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.
Clinical whole-exome sequencing has proven diagnostic utility; however, currently many clinicians have concerns regarding interpretation of results, insurance coverage, and cost.
临床实验室于2011年开始提供全外显子组测序服务，费用在4500美元至9000美元之间。报道的有害突变检测率在25%至50%之间。根据我们临床遗传学服务的经验，实际成功率可能低于估计率。我们报告了我们自己的经验结果以及对临床遗传学家的一项调查结果，以确定：（i）临床环境中致病基因检测的当前成功率；（ii）是否存在保险授权问题；（iii）临床实验室给出的周转时间是否准确；我们还评估了医疗服务提供者对临床全外显子组测序的看法。
我们回顾了我们的结果以及一项以电子方式分发给47个临床遗传学中心的调查结果。
总共获得了35份外显子组报告。如果将所有阳性结果整理在一起，我们观察到成功率为22.8%。有一个结果错误地将一个已知的良性变异鉴定为致病变异。一些保险公司承保了所有检测，而其他保险公司则拒绝提供任何保险覆盖。我们的报告中只有三份（23.1%）在实验室给出的周转时间内完成。在我们的调查中，超过50%的临床医生目前没有订购全外显子组测序，许多人表示担心结果的解读、保险覆盖范围和费用。
临床全外显子组测序已证明具有诊断效用；然而，目前许多临床医生对结果解读、保险覆盖范围和费用存在担忧。
