ArticleGenome research2015
Actionable exomic incidental findings in 6503 participants: challenges of variant classification.
3 registry-linked trialsOpen access · bronzeAbstract read
In one paragraph
Article in Genome research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 226 papers, 12 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
226citing papers in PubMed, 12 pooled it
–field-weighted citation impact
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2
NCT05687578 enrolling by invitationnot on this mapstarted 2023, after this paper: background citation
A Prospective, Non-Randomized, Multi-Center Observational Study to Establish a Physical Baseline Profile for Individual Study Subjects Using Various Modalities and Identify Deviations Via Longitudinal Monitoring That May Develop Over Time
NCT06802029 enrolling by invitationnot on this mapstarted 2025, after this paper: background citation
A Prospective, Non-Randomized, Multi-Center Observational Study to Establish a Physical Baseline Profile for Individual Study Subjects Using Various Modalities and Identify Deviations Via Longitudinal Monitoring for Participants Ages 6 Through 18
Who cites it
226 citing papers in PubMed, 12 syntheses or guidelines pooled it, 361 citations in OpenAlex.
- Genome-wide meta-analysis of quantitatively measured generalized anxiety symptoms in individuals of European ancestry.Nature human behaviour · 2026Pooled it
- Multi-ancestry meta-analysis of keloids uncovers novel susceptibility loci in diverse populations.Nature communications · 2025Pooled it
- Secondary findings in hereditary cancer genes after germline genetic testing - systematic review of literature.Human genetics · 2025Pooled it
- Cross-ancestry analyses of Chinese and European populations reveal insights into the genetic architecture and disease implication of metabolites.Cell genomics · 2025Pooled it
- Genome-wide meta-analysis of myasthenia gravis uncovers new loci and provides insights into polygenic prediction.Nature communications · 2024Pooled it
- A genome-wide meta-analysis identifies 50 genetic loci associated with carpal tunnel syndrome.Nature communications · 2022Pooled it
- Genome-wide association meta-analyses identify novel genetic risk loci and polygenic phenotype associations for heroin, methamphetamine and alcohol dependences.Clinical and translational medicine · 2022Pooled it
- Precision medicine in women with epilepsy: The challenge, systematic review, and future direction.Epilepsy & behavior : E&B · 2021Pooled it
- 2020 APHRS/HRS expert consensus statement on the investigation of decedents with sudden unexplained death and patients with sudden cardiac arrest, and of their families.Heart rhythm · 2021Guideline
- Genetic variants of calcium and vitamin D metabolism in kidney stone disease.Nature communications · 2019Pooled it
- Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer's disease risk.Nature genetics · 2019Pooled it
- Predicting Functional Effects of Synonymous Variants: A Systematic Review and Perspectives.Frontiers in genetics · 2019Pooled it
- ORCA, a values-based decision aid for selecting additional findings from genomic sequencing in adults: Efficacy results from a randomized trial.Genetics in medicine : official journal of the American College of Medical Genetics · 2022Trial
- Prediction of Genotype Positivity in Patients With Hypertrophic Cardiomyopathy Using Machine Learning.Circulation. Genomic and precision medicine · 2021Trial
- Clinical exome sequencing vs. usual care for hereditary colorectal cancer diagnosis: A pilot comparative effectiveness study.Contemporary clinical trials · 2019Trial
- Rare loss of function variants in candidate genes and risk of colorectal cancer.Human genetics · 2018Trial
- Design of a randomized controlled trial for genomic carrier screening in healthy patients seeking preconception genetic testing.Contemporary clinical trials · 2017Trial
- Article
- Genetic interconnections between personality-related phenotypes and psychiatric disorders.European archives of psychiatry and clinical neuroscience · 2026Article
- Genetic overlap and shared risk loci between autism spectrum disorder and cardiometabolic traits.Molecular psychiatry · 2026Article
166 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
73 authors at 20 institutions in 1 country.
Laura M AmendolaDepartment of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington 98195, USA;
Michael O DorschnerDepartment of Genome Sciences, University of Washington, Seattle, Washington 98195, USA; Department of Laboratory Medicine, University of Washington, Seattle, Washington 98195, USA; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington 98195, USA;
Peggy D RobertsonDepartment of Genome Sciences, University of Washington, Seattle, Washington 98195, USA;
Joseph S SalamaDepartment of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington 98195, USA;
Ragan HartDepartment of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington 98195, USA;
Brian H ShirtsDepartment of Laboratory Medicine, University of Washington, Seattle, Washington 98195, USA;
Mitzi L MurrayDepartment of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington 98195, USA; Department of Pathology, University of Washington, Seattle, Washington 98195, USA;
Mari J TokitaDepartment of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington 98195, USA;
Carlos J GallegoDepartment of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington 98195, USA;
Daniel Seung KimDepartment of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington 98195, USA; Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA;
James T BennettDepartment of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington 98195, USA; Department of Pediatrics, University of Washington, Seattle, Washington 98195, USA;
David R CrosslinDepartment of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington 98195, USA; Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA;
Jane RanchalisDepartment of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington 98195, USA;
Kelly L JonesDepartment of Pediatrics, University of Washington, Seattle, Washington 98195, USA;
Elisabeth A RosenthalDepartment of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington 98195, USA;
Ella R JarvikDepartment of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington 98195, USA;
Andy ItsaraDepartment of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington 98195, USA;
Emily H TurnerDepartment of Genome Sciences, University of Washington, Seattle, Washington 98195, USA; Department of Laboratory Medicine, University of Washington, Seattle, Washington 98195, USA;
Daniel S HermanDepartment of Laboratory Medicine, University of Washington, Seattle, Washington 98195, USA;
Jennifer SchleitDepartment of Pathology, University of Washington, Seattle, Washington 98195, USA;
Amber BurtDepartment of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington 98195, USA;
Seema M JamalDepartment of Pediatrics, Division of Genetic Medicine, University of Washington, Seattle, Washington 98195, USA;
Jenica L AbrudanDepartment of Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA; Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA;
Andrew D JohnsonThe Framingham Heart Study, Division of Intramural Research, National Heart, Lung and Blood Institute, Framingham, Massachusetts 01702, USA;
Laura K ConlinDepartment of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA;
Matthew C DulikDepartment of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA; Department of Pediatrics, Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA;
Avni SantaniDepartment of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA;
Danielle R MettervilleLaboratory of Molecular Medicine, Partners Healthcare, Boston, Massachusetts 02115, USA;
Melissa KellyPartners Healthcare Personalized Medicine, Partners Healthcare, Boston, Massachusetts 02115, USA;
Ann Katherine M ForemanDepartment of Genetics, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA;
Kristy LeeDepartment of Genetics, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA;
Kent D TaylorTranslational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics at Harbor-UCLA, Torrence, California 90502, USA;
Xiuqing GuoTranslational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics at Harbor-UCLA, Torrence, California 90502, USA;
Kristy CrooksDepartment of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27514, USA;
Lesli A KiedrowskiDepartment of Cancer Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA;
Leslie J RaffelMedical Genetics Research Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA;
Ora GordonMedical Genetics Research Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA;
Kalotina MachiniLaboratory of Molecular Medicine, Partners Healthcare, Boston, Massachusetts 02115, USA; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA; Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA;
Robert J DesnickDepartment of Genetic and Genomic Medicine, Division of Medical Genetics, Mount Sinai Hospital, New York, New York 10029, USA;
Leslie G BieseckerGenetic Diseases Research Branch, National Human Genome Research Institute, Bethesda, Maryland 20892, USA;
Steven A LubitzCardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA;
Surabhi MulchandaniDepartment of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA;
Greg M CooperHudsonAlpha Institute for Biotechnology, Huntsville, Alabama 35806, USA;
Steven JoffeDepartment of Medical Ethics and Health Policy, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, USA;
C Sue RichardsDepartment of Molecular and Medical Genetics, Oregon Health and Science University, Portland, Oregon 97239, USA;
Yaoping YangDepartment of Pediatrics, Division of Infectious Disease, Los Angeles Biomedical Research Institute and Department of Pediatrics at Harbor-UCLA, Torrence, California 90502, USA;
Jerome I RotterTranslational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics at Harbor-UCLA, Torrence, California 90502, USA;
Stephen S RichCenter for Public Health Genomics, University of Virginia, Charlottesville, Virginia 22908, USA;
Christopher J O'DonnellThe Framingham Heart Study, Division of Intramural Research, National Heart, Lung and Blood Institute, Framingham, Massachusetts 01702, USA; Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA;
Jonathan S BergDepartment of Genetics, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA;
Nancy B SpinnerDepartment of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA;
James P EvansDepartment of Genetics, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA;
Stephanie M FullertonDepartment of Bioethics and Humanities, University of Washington, Seattle, Washington 98195, USA;
Kathleen A LeppigGenetic Services, Group Health Cooperative, Seattle, Washington 98112, USA;
Robin L BennettDepartment of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington 98195, USA;
Thomas BirdDepartment of Neurology, University of Washington, Seattle, Washington 98195, USA; Veterans Affairs Puget Sound Health Care System Geriatric Research, Education, and Clinical Center, Seattle, Washington 98108, USA;
Virginia P SybertDepartment of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington 98195, USA; Dermatology, Group Health Cooperative, Seattle, Washington 98112, USA;
William M GradyClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA; Department of Medicine, Division of Gastroenterology, University of Washington, Seattle, Washington 98195, USA;
Holly K TaborDepartment of Pediatrics, University of Washington, Seattle, Washington 98195, USA; Treuman Katz Center for Pediatric Bioethics, Seattle Children's Research Institute, Seattle, Washington 98105, USA;
Jerry H KimDepartment of Anesthesiology and Pain Medicine, University of Washington, Seattle, Washington 98195, USA;
Michael J BamshadDepartment of Genome Sciences, University of Washington, Seattle, Washington 98195, USA; Department of Pediatrics, University of Washington, Seattle, Washington 98195, USA;
Benjamin WilfondTreuman Katz Center for Pediatric Bioethics, Seattle Children's Research Institute, Seattle, Washington 98105, USA; Department of Pediatrics, Division of Bioethics, University of Washington, Seattle, Washington 98195, USA.
Arno G MotulskyDepartment of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington 98195, USA; Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA;
C Ronald ScottDepartment of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington 98195, USA; Department of Pediatrics, Division of Genetic Medicine, University of Washington, Seattle, Washington 98195, USA;
Colin C PritchardDepartment of Laboratory Medicine, University of Washington, Seattle, Washington 98195, USA;
Tom D WalshDepartment of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington 98195, USA;
Wylie BurkeDepartment of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington 98195, USA; Department of Bioethics and Humanities, University of Washington, Seattle, Washington 98195, USA;
Wendy H RaskindDepartment of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington 98195, USA; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington 98195, USA;
Peter ByersDepartment of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington 98195, USA; Department of Pathology, University of Washington, Seattle, Washington 98195, USA;
Fuki M HisamaDepartment of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington 98195, USA;
Heidi RehmLaboratory of Molecular Medicine, Partners Healthcare, Boston, Massachusetts 02115, USA; Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA;
Debbie A NickersonDepartment of Genome Sciences, University of Washington, Seattle, Washington 98195, USA;
Gail P JarvikDepartment of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington 98195, USA; Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA;
University of Washington · USUniversity of Washington Medical Center · USChildren's Hospital of Philadelphia · USUniversity of North Carolina at Chapel Hill · USThe Lundquist Institute · USCedars-Sinai Medical Center · USGroup Health Cooperative · USMassachusetts General Hospital · USMass General Brigham · USSeattle Children's Hospital · USBrigham and Women's Hospital · USCancer Genetics (United States) · USHarvard University · USHudsonAlpha Institute for Biotechnology · USMount Sinai Medical Center · USNational Heart Lung and Blood Institute · USNational Institutes of Health · USOregon Health & Science University · USUniversity of Pennsylvania · USUniversity of Virginia Health System · US
Funding
Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Thomas James Lynch · 1985 to 2026
$296.4MUCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0MTransgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ALAN R. SALTIEL · 2003 to 2026
$40.4MUniversity of Washington Medical Scientist Training Program: MD/PhDT32GM007266 · NIGMS · UNIVERSITY OF WASHINGTON · PI HORWITZ, MARSHALL S. · 1985 to 2023
$30.4MResource ProjectU41HG006834 · NHGRI · BRIGHAM AND WOMEN'S HOSPITAL · PI REHM, HEIDI L · 2013 to 2020
$26.9MCardiovascular Genomics and Bioinformatics projectsZIAHL006170 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI JOHNSON, ANDREW · 2013 to 2025
$25.3MNorth Carolina Clinical Genomic Evaluation by Next-gen Exome Sequencing 2U01HG006487 · NHGRI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BERG, JONATHAN S, POWELL, BRADFORD C. · 2012 to 2021
$22.7MMeasuring Perceptions of Utility of Clinical Genome Sequencing: Instrument Testing and ValidationU01HG006485 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI MCGUIRE, AMY L, PARSONS, DONALD W. · 2012 to 2021
$22.1MGenomic Ascertainment - Molecular and Genetic AspectsZIAHG200359 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI BIESECKER, LESLIE · 2009 to 2025
$19.7MGenomic Ascertainment - Clinical and Behavioral AspectsZIAHG200387 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI BIESECKER, LESLIE · 2013 to 2025
$15.5MIntegration of Whole Genome Sequencing into Clinical MedicineU01HG006500 · NHGRI · BRIGHAM AND WOMEN'S HOSPITAL · PI GREEN, ROBERT C. · 2012 to 2016
$11.5MNorthwest Genomics CenterRC2HL102926 · NHLBI · UNIVERSITY OF WASHINGTON · PI GREEN, PHILIP P, NICKERSON, DEBORAH A · 2009 to 2009
$11.0MNCATS NIH HHS UL1 TR000124NCI NIH HHS 5P30CA015704NCI NIH HHS P30 CA015704NCI NIH HHS R01 CA175716NHGRI NIH HHS U01 HG006375NHGRI NIH HHS U01HG006375NHGRI NIH HHS U01 HG006485NHGRI NIH HHS U01HG006485NHGRI NIH HHS U01 HG006487NHGRI NIH HHS U01HG006487NHGRI NIH HHS U01 HG006492NHGRI NIH HHS U01HG006492NHGRI NIH HHS U01 HG006500NHGRI NIH HHS U01HG006500NHGRI NIH HHS U01 HG006507NHGRI NIH HHS U01 HG006546NHGRI NIH HHS U01HG006546NHGRI NIH HHS U01 HG007307NHGRI NIH HHS U01HG007307NHGRI NIH HHS U41 HG006834NHGRI NIH HHS U41HG006834NHGRI NIH HHS UM1 HG007292NHGRI NIH HHS UM1HG007292NHGRI NIH HHS UM1 HG007301NHGRI NIH HHS UM1HG007301NHLBI NIH HHS 1K23HL114724NHLBI NIH HHS K23 HL114724NHLBI NIH HHS RC2 HL-102923NHLBI NIH HHS RC2 HL102923NHLBI NIH HHS RC2 HL-102924NHLBI NIH HHS RC2 HL102924NHLBI NIH HHS RC2 HL-102925NHLBI NIH HHS RC2 HL102925NHLBI NIH HHS RC2 HL-102926NHLBI NIH HHS RC2 HL102926NHLBI NIH HHS RC2 HL-103010NHLBI NIH HHS RC2 HL103010NIA NIH HHS R01 AG033193NIA NIH HHS U01 AG049505NIDDK NIH HHS P30 DK063491NIGMS NIH HHS T32 GM007266NIGMS NIH HHS T32 GM007454PHS HHS NHGRI/NCI U01HG006507PHS HHS NIH/NIGMS T32 GM007454
Abstract
Recommendations for laboratories to report incidental findings from genomic tests have stimulated interest in such results. In order to investigate the criteria and processes for assigning the pathogenicity of specific variants and to estimate the frequency of such incidental findings in patients of European and African ancestry, we classified potentially actionable pathogenic single-nucleotide variants (SNVs) in all 4300 European- and 2203 African-ancestry participants sequenced by the NHLBI Exome Sequencing Project (ESP). We considered 112 gene-disease pairs selected by an expert panel as associated with medically actionable genetic disorders that may be undiagnosed in adults. The resulting classifications were compared to classifications from other clinical and research genetic testing laboratories, as well as with in silico pathogenicity scores. Among European-ancestry participants, 30 of 4300 (0.7%) had a pathogenic SNV and six (0.1%) had a disruptive variant that was expected to be pathogenic, whereas 52 (1.2%) had likely pathogenic SNVs. For African-ancestry participants, six of 2203 (0.3%) had a pathogenic SNV and six (0.3%) had an expected pathogenic disruptive variant, whereas 13 (0.6%) had likely pathogenic SNVs. Genomic Evolutionary Rate Profiling mammalian conservation score and the Combined Annotation Dependent Depletion summary score of conservation, substitution, regulation, and other evidence were compared across pathogenicity assignments and appear to have utility in variant classification. This work provides a refined estimate of the burden of adult onset, medically actionable incidental findings expected from exome sequencing, highlights challenges in variant classification, and demonstrates the need for a better curated variant interpretation knowledge base.
Indexed as
ExomeGenomicsIncidental FindingsAdultBlack PeopleFemaleGene FrequencyGenes, DominantGenetic Association StudiesGenetic TestingGenome, HumanHigh-Throughput Nucleotide SequencingHumansMalePhenotypePolymorphism, Single Nucleotide
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.