Sep 24, 2013

Actionable, pathogenic incidental findings in 1,000 participants' exomes

American Journal of Human Genetics
Michael O DorschnerGail P Jarvik

Abstract

The incorporation of genomics into medicine is stimulating interest on the return of incidental findings (IFs) from exome and genome sequencing. However, no large-scale study has yet estimated the number of expected actionable findings per individual; therefore, we classified actionable pathogenic single-nucleotide variants in 500 European- and 500 African-descent participants randomly selected from the National Heart, Lung, and Blood Institute Exome Sequencing Project. The 1,000 individuals were screened for variants in 114 genes selected by an expert panel for their association with medically actionable genetic conditions possibly undiagnosed in adults. Among the 1,000 participants, 585 instances of 239 unique variants were identified as disease causing in the Human Gene Mutation Database (HGMD). The primary literature supporting the variants' pathogenicity was reviewed. Of the identified IFs, only 16 unique autosomal-dominant variants in 17 individuals were assessed to be pathogenic or likely pathogenic, and one participant had two pathogenic variants for an autosomal-recessive disease. Furthermore, one pathogenic and four likely pathogenic variants not listed as disease causing in HGMD were identified. These data can provid...Continue Reading

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  • Citations149

References

  • References24
  • Citations149

Citations

Mentioned in this Paper

TP53 gene
LDLR wt Allele
BRCA2 Protein
Nemaline Myopathy 3
TMEM43 gene
SERPINA1 gene
Lung
Genome
Pathogenic Organism
Medical Genetics Specialty

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