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Whole Exome Sequencing: How is it being used?

Fifty years after the structure of DNA was initially described, the first reference human genome was completed by the Human Genome Project in 2003.  Since then, genomic sequencing technology, particularly next-generation sequencing (NGS), has revolutionized the genomic testing industry. NGS technology has not only allowed for gene discovery but has also provided a platform for large-scale genomic analyses, such as clinical exome and genome sequencing.  

Whole exome sequencing (WES) is a genetic analysis technique that identifies and aligns the parts of the genome that code for proteins (called the exome).  Detecting each DNA base is only part of the assay; WES also requires putting those bases in order- or “sequencing.”  On

ly then, can variations in DNA be appreciated and interpreted.  WES was first used in patients to identify genetic causes of disease in 2009. In the subsequent decade, WES has become a valuable tool for providers in the diagnosis and treatment of some genetic disorders. 

WES is used mostly by geneticists (60-61%), followed by neurologists (22%), and other non-genetics specialists1.  Evaluating WES use is ever important, considering the expansion of this complex genetic test into other areas of medicine, including rheumatology, infectious disease, and even chiropractic practice. Lessons learned from WES are likely to translate to whole-genome sequencing (WGS), which is also increasing in popularity. WGS, like WES, is large scale sequencing of genomic material but differs in that all genomic material is sequenced. Though it is more costly, time-consuming, and complex, WGS holds promise for increased detection of disease-causing variations with one comprehensive test. 

InformedDNA studied two years of WES prior authorization requests from seven regional health plans between March 1, 2018, to March 1, 2020, when COVID-19 just started making an impact. There were 450 WES requests. All of the health plans used the same clinical guidelines written with oversight from InformedDNA genetics experts. 

  • Of the 450 requests, 241 (54%) were ultimately approved, meeting health plan coverage criteria for WES.  
  • Of the 209 (46%) requests which were not approved, the most common reason for denial was that there was only one organ system involved with no other coverage criteria met.  
Who is ordering whole exome sequencing?

The trends in our analysis mirrored those from a previous study from 2016, with genetics specialists ordering WES most frequently, followed by neurology. In the current analysis, we found that:

  • Genetics providers ordered 64% of the WES tests;
  • Neurologists ordered 19%;
  • Pediatrics accounted for 7%;
  • OBGYN/MFM providers ordered 2.4%;
  • And, providers from various other specialties accounted for the remaining 7%. 
Where does genetic counseling fit with WES testing?

In our review, we probed further to determine if clinical genetic counselors were involved in the WES test requests. We were able to confirm that a clinical genetic counselor was involved in 312 (69%) of requests. Requests were more likely to be approved/meet coverage criteria when genetic counselors were involved (P=.002659). Of the 312 cases for which a genetic counselor was involved, 67% of those were ultimately approved/met coverage criteria. One might think that genetic counselors were only involved in WES requests ordered by genetics providers. However, 33% of the requests with genetic counselor involvement were ordered by non-genetics specialists, demonstrating the growth and impact of clinical genetic counselors in other specialties across healthcare.  

Takeaways:
  • WES continues to be a valuable tool for the diagnosis and treatment of genetic disorders, and health plans are covering this test more frequently than in the past. 
  • WES is utilized by both genetics and non-genetics specialists.
  • Genetic counselors are important participants in the WES testing process, involved in many cases for tests ordered by non-genetics healthcare providers.
  • Coverage criteria are more likely to be met in cases facilitated by genetic counselors. 

At InformedDNA, we leverage the expertise of the largest, most experienced, fully employed staff of lab-independent, board-certified genetics specialists in the U.S. to help ensure that patients, health plans, health systems, hospitals, pharmaceutical companies, and healthcare providers all have access to the highest quality genetics expertise and services. To learn more about our services, just submit the short form below and we’ll get back to you right away. Or, give us a call at 844-846-3763.

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  1. Fraley et al., 2016 and Posey et al., 2016