Practices and Policies of Clinical Exome Sequencing Providers: Analysis and Implications

Abstract

Exome and whole genome sequencing (ES/WGS) offer potential advantages over traditional approaches to diagnostic genetic testing. Consequently, use of ES/WGS in clinical settings is rapidly becoming commonplace. Yet there are myriad moral, ethical, and perhaps legal implications attached to the use of ES and health care professionals and institutions will need to consider these implications in the context of the varied practices and policies of ES service providers. We developed "core elements" of content and procedures for informed consent, data sharing, and results management and a quantitative scale to assess the extent to which research protocols met the standards established by these core elements. We then used these tools to evaluate the practices and policies of each of the 6 U.S. CLIA-certified labs offering clinical ES. Approaches toward informed consent, data sharing, and results return vary widely among ES providers as do the overall potential merits and disadvantages of each, and more importantly, the balance between the two.

A Review of Consent Practices and Perspectives for Pharmacogenetic testing

“…A recent comparison of written consent forms for genetic testing also showed variability in the type of information disclosed, with several laboratories using the same consent form for single and panel-based testing [54,55]. Despite concerns about incidental findings and its prominence with the use of genomic tests (whole genome or exome testing [54][55][56]; chromosomal microarrays arrays [57]), this potential was only disclosed by three laboratories. Perhaps due to the use of more targeted testing platforms (i.e., genotyping for common variants), the issue of incidental findings is of less concern for PGx testing.…”

Current practices and guidelines for clinical next-generation sequencing oncology testing

“…As neither approach is simple or inexpensive to implement, many laboratories eschew such confirmatory testing during routine analysis. While PCR-based dideoxy sequencing ("Sanger" sequencing) is a generally accepted method of confirmatory testing for constitutional clinical NGS [17][18][19][20] , its sensitivity is limited to approximately 10%-20% VAF. As cancer NGS testing routinely identifies clinically relevant mutations from 5%-10% VAF, it Sanger is not an ideal method for confirmation for all variants.…”

High diagnostic yield of clinical exome sequencing in Middle Eastern patients with Mendelian disorders

“…In contrast to whole-genome sequencing (WGS), whole-exome sequencing (WES) focuses on the ~2 % of the genome that is protein coding, thus reducing cost and easing interpretation (Bick and Dimmock 2011). The successful use of WES in the research setting to identify causal mutations in challenging medical conditions was quickly translated into its rapid incorporation in molecular diagnostics (clinical exome sequencing or CES) (Jamal et al 2013). The first large-scale study to assess the diagnostic yield of CES was in 2013 and reported a yield of ~25 %, mostly in patients with neurodevelopmental disorders (Yang et al 2013).…”