Literature DB >> 24525916

Clinical whole-exome sequencing: are we there yet?

Paldeep Singh Atwal1, Marie-Louise Brennan1, Rachel Cox1, Michael Niaki1, Julia Platt1, Margaret Homeyer1, Andrea Kwan1, Sylvie Parkin1, Susan Schelley1, Leah Slattery1, Yael Wilnai1, Jonathan Adam Bernstein1, Gregory M Enns1, Louanne Hudgins1.   

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.
CONCLUSION: Clinical whole-exome sequencing has proven diagnostic utility; however, currently many clinicians have concerns regarding interpretation of results, insurance coverage, and cost.

Entities:  

Mesh:

Year:  2014        PMID: 24525916     DOI: 10.1038/gim.2014.10

Source DB:  PubMed          Journal:  Genet Med        ISSN: 1098-3600            Impact factor:   8.822


  28 in total

Review 1.  Clinical exome sequencing in neurologic disease.

Authors:  Brent L Fogel; Saty Satya-Murti; Bruce H Cohen
Journal:  Neurol Clin Pract       Date:  2016-04

Review 2.  Can genomic medicine improve financial sustainability of health systems?

Authors:  Christine Y Lu; Joshua P Cohen
Journal:  Mol Diagn Ther       Date:  2015-04       Impact factor: 4.074

3.  Insurance companies are slow to cover next-generation sequencing.

Authors:  Shraddha Chakradhar
Journal:  Nat Med       Date:  2015-03       Impact factor: 53.440

4.  Analysis of VUS reporting, variant reinterpretation and recontact policies in clinical genomic sequencing consent forms.

Authors:  Danya F Vears; Emilia Niemiec; Heidi Carmen Howard; Pascal Borry
Journal:  Eur J Hum Genet       Date:  2018-08-24       Impact factor: 4.246

5.  Genome-wide identification of CBX2 targets: insights in the human sex development network.

Authors:  Wassim Eid; Lennart Opitz; Anna Biason-Lauber
Journal:  Mol Endocrinol       Date:  2015-01-08

6.  Yield of whole exome sequencing in undiagnosed patients facing insurance coverage barriers to genetic testing.

Authors:  Chloe M Reuter; Jennefer N Kohler; Devon Bonner; Diane Zastrow; Liliana Fernandez; Annika Dries; Shruti Marwaha; Jean Davidson; Elly Brokamp; Matthew Herzog; Joyce Hong; Ellen Macnamara; Jill A Rosenfeld; Kelly Schoch; Rebecca Spillmann; Joseph Loscalzo; Joel Krier; Joan Stoler; David Sweetser; Christina G S Palmer; John A Phillips; Vandana Shashi; David A Adams; Yaping Yang; Euan A Ashley; Paul G Fisher; John J Mulvihill; Jonathan A Bernstein; Matthew T Wheeler
Journal:  J Genet Couns       Date:  2019-09-03       Impact factor: 2.537

7.  Exploring the Issues Surrounding Clinical Exome Sequencing in the Prenatal Setting.

Authors:  Swetha Narayanan; Bruce Blumberg; Marla L Clayman; Vivian Pan; Catherine Wicklund
Journal:  J Genet Couns       Date:  2018-03-10       Impact factor: 2.537

8.  Personalized sequencing and the future of medicine: discovery, diagnosis and defeat of disease.

Authors:  Edward D Esplin; Ling Oei; Michael P Snyder
Journal:  Pharmacogenomics       Date:  2014-11       Impact factor: 2.533

9.  Clinical and Counseling Experiences of Early Adopters of Whole Exome Sequencing.

Authors:  Shubhangi Arora; Eden Haverfield; Gabriele Richard; Susanne B Haga; Rachel Mills
Journal:  J Genet Couns       Date:  2015-08-19       Impact factor: 2.537

Review 10.  Genome-Wide Sequencing for Prenatal Detection of Fetal Single-Gene Disorders.

Authors:  Ignatia B van den Veyver; Christine M Eng
Journal:  Cold Spring Harb Perspect Med       Date:  2015-08-07       Impact factor: 6.915

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