Journal article
ClinGen recuration of hearing loss associated-genes demonstrates significant changes in gene-disease validity over time
Genetics in medicine, Vol.27(5), 101392
05/2025
DOI: 10.1016/j.gim.2025.101392
PMCID: PMC12170156
PMID: 39987489
Abstract
The ClinGen Hearing Loss Gene Curation Expert Panel (GCEP) was assembled in 2016 and has since curated 174 gene-disease relationships (GDRs) using ClinGen’s semi-quantitative framework. ClinGen mandates timely recuration of all GDRs classified as Disputed, Limited, Moderate, and Strong, every 2–3 years.
Thirty-five GDRs met the criteria for recuration within two years of original curation. Previous evidence was reevaluated using the latest curation guidelines and a comprehensive literature review was performed for new evidence. The recurations were approved by the GCEP and published to the ClinGen website (www.clinicalgenome.org).
Eight out of 35 (22%) GDRs changed classification. Two Moderate and five Strong GDRs upgraded to Definitive due to new case evidence. One Strong was subsumed under another Definitive GDR, after evaluation of lumping/splitting of disease entities. Twenty-seven out of 35 remained unchanged with little to no new evidence reported.
Genes classified as Moderate and Strong are likely to build evidence and change in classification over time, whereas Limited are unlikely to gain evidence. These findings also highlight the critical role of recuration in ensuring that genetic tests and research studies incorporate the most up-to-date evidence into their efforts.
Details
- Title: Subtitle
- ClinGen recuration of hearing loss associated-genes demonstrates significant changes in gene-disease validity over time
- Creators
- Kezang C Tshering - Broad InstituteMarina T DiStefano - Broad InstituteAndrea M Oza - Broad InstitutePamela Ajuyah - Broad InstituteRyan Webb - Broad InstituteEnyonam Edoh - Broad InstituteKevin TA Booth - Indiana University School of MedicineRichard J. Smith - University of Iowa, OtolaryngologyHela Azaiez - University of IowaClinGen Hearing Loss Clinical Domain Working Group
- Resource Type
- Journal article
- Publication Details
- Genetics in medicine, Vol.27(5), 101392
- DOI
- 10.1016/j.gim.2025.101392
- PMID
- 39987489
- PMCID
- PMC12170156
- NLM abbreviation
- Genet Med
- ISSN
- 1098-3600
- eISSN
- 1530-0366
- Publisher
- Elsevier Inc; NEW YORK
- Grant note
- National Human Genome Research Institute of the National Institutes of Health: U24HG006834
This study was funded by the National Human Genome Research Institute of the National Institutes of Health (grant number U24HG006834) . The content is solely the re-sponsibility of the authors and does not represent the of fi cial view of the National Institutes of Health.
- Language
- English
- Electronic publication date
- 02/19/2025
- Date published
- 05/2025
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine
- Record Identifier
- 9984793977702771
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