Evidence map›Paper›PMID 39987489›Full record

ArticleGenetics in medicine : official journal of the American College of Medical Genetics2025

ClinGen recuration of hearing loss-associated genes demonstrates significant changes in gene-disease validity over time.

Kezang C Tshering, Marina T DiStefano, Andrea M Oza, Pamela Ajuyah, Ryan Webb, Enyonam Edoh, Ellie Broeren, Julie Ratliff, Vanessa Gitau, Kelley Paris and 34 more

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. medRxiv : the preprint server for health sciences · 2026
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

44 authors.

Kezang C TsheringThe Broad Institute of MIT and Harvard, Cambridge, MA.
Marina T DiStefanoThe Broad Institute of MIT and Harvard, Cambridge, MA; Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, Cambridge, MA.
Andrea M OzaThe Broad Institute of MIT and Harvard, Cambridge, MA.
Pamela AjuyahThe Broad Institute of MIT and Harvard, Cambridge, MA.
Ryan WebbThe Broad Institute of MIT and Harvard, Cambridge, MA.
Enyonam EdohThe Broad Institute of MIT and Harvard, Cambridge, MA.
Ellie BroerenThe Broad Institute of MIT and Harvard, Cambridge, MA.
Julie RatliffThe Broad Institute of MIT and Harvard, Cambridge, MA.
Vanessa GitauThe Broad Institute of MIT and Harvard, Cambridge, MA.
Kelley ParisThe Broad Institute of MIT and Harvard, Cambridge, MA.
Amal AburyyanDepartment of Medicine, University of Washington, Seattle, WA.
John AlexanderMyriad Women's Health, South San Francisco, CA.
Victoria AlbanoDepartment of Otolaryngology & Communication Enhancement, Boston Children's Hospital, Boston, MA.
Donglin BaiDepartment of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
Kevin T A BoothDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN; Department of Otolaryngology-Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, IN.
Paula I BuonfiglioLaboratorio de Fisiología y Genética de la Audición. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres" (INGEBI), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
Cherine CharfeddineLaboratory of Biomedical Genomics and Oncogenetics, Institute Pasteur of Tunis, University of Tunis El Manar, Tunis, Tunisia; Université de la Manouba, Institut de Biotechnologie de Sidi-Thabet, Ariana, Tunisia.
Viviana DalamónLaboratorio de Fisiología y Genética de la Audición. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres" (INGEBI), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
Ignacio Del CastilloServicio de Genética, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos III (CB06/07/0048; CIBERER-ISCIII), Madrid, Spain.
Miguel Angel Moreno-PelayoServicio de Genética, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos III (CB06/07/0048; CIBERER-ISCIII), Madrid, Spain.
Hatice DuzkaleColor Health, Burlingame, CA.
Ben DorshorstPrevention Genetics, Marshfield, WI.
Rabia FaridiLaboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD.
Margaret KennaDepartment of Otolaryngology & Communication Enhancement, Boston Children's Hospital, Boston, MA.
Morag A LewisWolfson Sensory, Pain and Regeneration Centre, King's College London, London, United Kingdom.
Minjie LuoDivision of Genomic Diagnostics, The Children's Hospital of Philadelphia, Philadelphia, PA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Yu LuInstitute of Rare Diseases, West China Hospital of Sichuan University, Chengdu, China.
Rahma MkaouarLaboratory of Biomedical Genomics and Oncogenetics, Institute Pasteur of Tunis, University of Tunis El Manar, Tunis, Tunisia.
Tatsuo MatsunagaDivision of Hearing and Balance Research, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.
Kiyomitsu NaraDivision of Hearing and Balance Research, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.
Arti PandyaDivision of Genetics and Metabolism, Department of Pediatrics, UNC School of Medicine, Chapel Hill, NC.
Shelby RedfieldDepartment of Medicine, University of Washington, Seattle, WA.
Isabelle RouxLaboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD.
Lisa A SchimmentiDepartments of Clinical Genomics, Mayo Clinic Enterprise, Rochester, MN.
Isabelle SchrauwenDepartment of Translational Neurosciences, University of Arizona College of Medicine Phoenix, Phoenix, AZ.
Sherin ShaabanDepartment of Pathology, University of Utah School of Medicine, Salt Lake City, UT; ARUP Laboratories, Salt Lake City, UT.
Jun ShenDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Barbara VonaInstitute of Human Genetics, University Medical Center Göttingen, Göttingen, Germany; Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Göttingen, Germany.
Richard J SmithMolecular Otolaryngology and Renal Research Laboratories (MORL), Department of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa City, IA.
Heidi L RehmThe Broad Institute of MIT and Harvard, Cambridge, MA; Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, Cambridge, MA.
Hela AzaiezMolecular Otolaryngology and Renal Research Laboratories (MORL), Department of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa City, IA.
Ahmad N Abou TayounGenomics Center of Excellence, Al Jalila Children's Specialty Hospital, Dubai Health, Dubai, United Arab Emirates; Center for Genomic Discovery, Mohammed Bin Rashid University, Dubai Health, Dubai, United Arab Emirates.
Sami S AmrLaboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, Cambridge, MA. Electronic address: samr@bwh.harvard.edu.
ClinGen Hearing Loss Clinical Domain Working Group

Funding

ClinGen AI Data Delivery SupplementU24HG006834 · NHGRI · BROAD INSTITUTE, INC. · PI Marina DiStefano, CHRISTA LESE MARTIN · 2021 to 2026
$26.7M
NHGRI NIH HHS U24 HG006834
6 · The paper itself

Abstract

purposeThe Clinical Genome Resource (ClinGen) Hearing Loss Gene Curation Expert Panel was assembled in 2016 and has since curated 174 gene-disease relationships (GDRs) using ClinGen's semiquantitative framework. ClinGen mandates the timely recuration of all GDRs classified as Disputed, Limited, Moderate, and Strong every 2 to 3 years.

methodsThirty-five GDRs met the criteria for recuration within 2 years of original curation. Previous evidence was reevaluated using the latest curation guidelines, and a comprehensive literature review was performed to obtain new evidence. Recurations were approved by the Gene Curation Expert Panel and published on the ClinGen website (www.clinicalgenome.org).

resultsEight of 35 GDRs (22%) changed their classification. Two Moderate and 5 Strong GDRs were upgraded to Definitive because of new case evidence. One Strong was subsumed under another Definitive GDR after evaluation of the lumping/splitting of disease entities. Twenty-seven of 35 patients remained unchanged, with little to no new evidence reported.

conclusionGenes classified as Moderate and Strong were likely to build evidence and change their classification over time, whereas Limited were unlikely to gain evidence. These findings highlight the critical role of recuration in ensuring that genetic tests and research studies incorporate the most recent evidence into their efforts.

Indexed as

Genetic Predisposition to DiseaseHearing LossDatabases, GeneticData CurationGenetic Association StudiesGenome, HumanHumansClinGenDeafnessGene curationGenetic diagnosisHearing loss

Identifiers

PMID39987489
PMCPMC12170156

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