Actionable, Pathogenic Incidental Findings in 1,000 Participants’ Exomes

摘要: The incorporation of genomics into medicine is stimulating interest on the return incidental findings (IFs) from exome and genome sequencing. However, no large-scale study has yet estimated number expected actionable per individual; therefore, we classified pathogenic single-nucleotide variants in 500 European- African-descent participants randomly selected National Heart, Lung, Blood Institute Exome Sequencing Project. 1,000 individuals were screened for 114 genes by an expert panel their association with medically genetic conditions possibly undiagnosed adults. Among participants, 585 instances 239 unique identified as disease causing Human Gene Mutation Database (HGMD). primary literature supporting variants' pathogenicity was reviewed. Of IFs, only 16 autosomal-dominant 17 assessed to be or likely pathogenic, one participant had two autosomal-recessive disease. Furthermore, four not listed HGMD identified. These data can provide estimate frequency (∼3.4% European descent ∼1.2% African descent) high-penetrance 23 disproportionately (17) versus (6) descent. process classifying these underscores need a more comprehensive diverse centralized resource curated information clinical use minimize health disparities genomic medicine.