Evidence map›Paper›PMID 37066275›Full record

ArticlemedRxiv : the preprint server for health sciences2023

Beyond gene-disease validity: capturing structured data on inheritance, allelic-requirement, disease-relevant variant classes, and disease mechanism for inherited cardiac conditions.

Katherine S Josephs, Angharad M Roberts, Pantazis Theotokis, Roddy Walsh, Philip J Ostrowski, Matthew Edwards, Andrew Fleming, Courtney Thaxton, Jason D Roberts, Melanie Care and 25 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

35 authors.

Katherine S JosephsNational Heart and Lung Institute, Imperial College London, London, UK.
Angharad M RobertsNational Heart and Lung Institute, Imperial College London, London, UK.
Pantazis TheotokisNational Heart and Lung Institute, Imperial College London, London, UK.
Roddy WalshAmsterdam University Medical Centre, University of Amsterdam, Heart Center, Department of Experimental Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands.
Philip J OstrowskiGreat Ormond Street Hospital NHS Foundation Trust, London, UK.
Matthew EdwardsClinical Genetics & Genomics Lab, Royal Brompton and Harefield Hospitals, Guy's and St Thomas' NHS Foundation Trust, London UK.
Andrew FlemingClinical Genetics & Genomics Lab, Royal Brompton and Harefield Hospitals, Guy's and St Thomas' NHS Foundation Trust, London UK.
Courtney ThaxtonDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Jason D RobertsPopulation Health Research Institute, McMaster University, and Hamilton Health Sciences, Hamilton, Ontario, Canada.
Melanie CareDepartment of Molecular Genetics, University of Toronto, Toronto, Canada.
Wojciech ZarebaClinical Cardiovascular Research Center, University of Rochester, Rochester, New York, USA.
Arnon AdlerDivision of Cardiology, Peter Munk Cardiac Centre, University Health Network and Department of Medicine, University of Toronto, Toronto, ON, Canada.
Amy C Sturm23andMe, Sunnyvale, California, Genomic Health.
Rafik TadrosCardiovascular Genetics Center, Montreal Heart Institute, and Faculty of Medicine, Université de Montréal.
Valeria NovelliUnit of Immunology and Functional Genomics, Centro Cardiologico Monzino IRCCS, Milano, Italy.
Emma OwensDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Lucas BronickiCHEO Research Institute, University of Ottawa, Ontario, Canada.
Olga JarinovaCHEO Research Institute, University of Ottawa, Ontario, Canada.
Bert CallewaertCenter for Medical Genetics, Ghent University Hospital.
Stacey PetersDepartment of Cardiology and Genomic Medicine, Royal Melbourne Hospital, Melbourne, Australia.
Tom LumbersBarts Health & University College London Hospitals NHS Trusts, London, UK.
Elizabeth JordanDivision of Human Genetics, The Ohio State University, Columbus, Ohio USA.
Babken AsatryanDepartment of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Neesha KrishnanCentre for Population Genomics, Garvan Institute of Medical Research, and UNSW Sydney, Sydney, Australia.
Ray E HershbergerDivision of Human Genetics, The Ohio State University, Columbus, Ohio USA.
C Anwar A ChahalCenter for Inherited Cardiovascular Diseases, WellSpan Health, Lancaster, PA USA.
Andrew P LandstromDepartment of Pediatrics and Cell Biology, Duke University School of Medicine, Durham, North Carolina, US.
Cynthia JamesJohns Hopkins Center for Inherited Heart Diseases, Department of Medicine, Johns Hopkins.
Elizabeth M McNallyCenter for Genetic Medicine, Dept of Medicine (Cardiology), Northwestern University Feinberg School of Medicine, Chicago, IL US.
Daniel P JudgeMedical University of South Carolina, Charleston, SC USA.
Peter van TintelenDepartment of Genetics, University Medical Center Utrecht, Utrecht, the Netherlands.
Arthur WildeAmsterdam UMC location University of Amsterdam, Department of Cardiology, Meibergdreef 9, Amsterdam, the Netherlands; Amsterdam Cardiovascular Sciences, Heart Failure and arrhythmias, Amsterdam, the Netherlands.
Michael GollobInherited Arrhythmia and Cardiomyopathy Program, Division of Cardiology, University of Toronto, Toronto ON Canada.
Jodie InglesCentre for Population Genomics, Garvan Institute of Medical Research, and UNSW Sydney, Sydney, Australia.
James S WareNational Heart and Lung Institute, Imperial College London, London, UK.

Funding

The Clinical Genome Resource – Advancing genomic medicine through biocuration and expert assessment of genes and variants at scaleU24HG009650 · NHGRI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI JONATHAN S BERG, Jessica Ezzell Hunter · 2021 to 2026
$30.0M
Cardiomyopathy Genomes ProjectR01HL128075 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI MCNALLY, ELIZABETH M, NOBREGA, MARCELO A. · 2015 to 2023
$5.3M
NHGRI NIH HHS U24 HG009650NHLBI NIH HHS R01 HL128075Wellcome Trust
6 · The paper itself

Abstract

Background: As availability of genomic testing grows, variant interpretation will increasingly be performed by genomic generalists, rather than domain-specific experts. Demand is rising for laboratories to accurately classify variants in inherited cardiac condition (ICC) genes, including as secondary findings. Methods: We analyse evidence for inheritance patterns, allelic requirement, disease mechanism and disease-relevant variant classes for 65 ClinGen-curated ICC gene-disease pairs. We present this information for the first time in a structured dataset, CardiacG2P, and assess application in genomic variant filtering. Results: For 36/65 gene-disease pairs, loss-of-function is not an established disease mechanism, and protein truncating variants are not known to be pathogenic. Using CardiacG2P as an initial variant filter allows for efficient variant prioritisation whilst maintaining a high sensitivity for retaining pathogenic variants compared with two other variant filtering approaches. Conclusions: Access to evidence-based structured data representing disease mechanism and allelic requirement aids variant filtering and analysis and is pre-requisite for scalable genomic testing.

Indexed as

allelic requirementdisease mechanismgene curationgenomic variant filteringinheritanceInherited cardiac conditionsvariant classificationvariant interpretation

Identifiers

PMID37066275
PMCPMC10104233

What OpenQuestion holds

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Registered trials

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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.