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Practical considerations in the clinical application of whole-exome sequencing.

Publication ,  Journal Article
Shashi, V; McConkie-Rosell, A; Schoch, K; Kasturi, V; Rehder, C; Jiang, YH; Goldstein, DB; McDonald, MT
Published in: Clin Genet
February 2016

Despite the exciting advent of whole-exome sequencing (WES) in medical genetics practices, the optimal interpretation of results requires further actions such as reconsidering clinical information and obtaining further laboratory testing. There are no published data to guide clinicians in this process. In a retrospective study on 93 patients who underwent clinical WES, we set out to assess and resolve these practical challenges. With the laboratories reporting a molecular diagnostic rate of 25.8%, the medical geneticists and the laboratories were 90% concordant in their interpretation of the WES results. Divergence occurred when the medical geneticist reconsidered clinical information and/or additional information regarding pathogenicity of a variant. Variants of uncertain significance were reported in 86% of patients, with 53.7% needing follow-up, such as additional laboratory tests and genotyping of family members. By layering clinical data (e.g. mode of inheritance and phenotypic fit) on to the laboratory results, we developed clinical categories for the WES results. These categories of definite diagnosis (14/93), likely diagnosis (8/93), possible diagnosis (13/93) and no diagnosis (58/93) could be used to convey results to patients uniformly. Our framework for a clinically informed interpretation of the results enhances the utility of WES within medical genetics practices.

Duke Scholars

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Published In

Clin Genet

DOI

EISSN

1399-0004

Publication Date

February 2016

Volume

89

Issue

2

Start / End Page

173 / 181

Location

Denmark

Related Subject Headings

  • Young Adult
  • Sequence Analysis, DNA
  • Middle Aged
  • Male
  • Infant, Newborn
  • Infant
  • Incidental Findings
  • Humans
  • Genetics & Heredity
  • Follow-Up Studies
 

Citation

APA
Chicago
ICMJE
MLA
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Shashi, V., McConkie-Rosell, A., Schoch, K., Kasturi, V., Rehder, C., Jiang, Y. H., … McDonald, M. T. (2016). Practical considerations in the clinical application of whole-exome sequencing. Clin Genet, 89(2), 173–181. https://doi.org/10.1111/cge.12569
Shashi, V., A. McConkie-Rosell, K. Schoch, V. Kasturi, C. Rehder, Y. H. Jiang, D. B. Goldstein, and M. T. McDonald. “Practical considerations in the clinical application of whole-exome sequencing.Clin Genet 89, no. 2 (February 2016): 173–81. https://doi.org/10.1111/cge.12569.
Shashi V, McConkie-Rosell A, Schoch K, Kasturi V, Rehder C, Jiang YH, et al. Practical considerations in the clinical application of whole-exome sequencing. Clin Genet. 2016 Feb;89(2):173–81.
Shashi, V., et al. “Practical considerations in the clinical application of whole-exome sequencing.Clin Genet, vol. 89, no. 2, Feb. 2016, pp. 173–81. Pubmed, doi:10.1111/cge.12569.
Shashi V, McConkie-Rosell A, Schoch K, Kasturi V, Rehder C, Jiang YH, Goldstein DB, McDonald MT. Practical considerations in the clinical application of whole-exome sequencing. Clin Genet. 2016 Feb;89(2):173–181.
Journal cover image

Published In

Clin Genet

DOI

EISSN

1399-0004

Publication Date

February 2016

Volume

89

Issue

2

Start / End Page

173 / 181

Location

Denmark

Related Subject Headings

  • Young Adult
  • Sequence Analysis, DNA
  • Middle Aged
  • Male
  • Infant, Newborn
  • Infant
  • Incidental Findings
  • Humans
  • Genetics & Heredity
  • Follow-Up Studies