Journal article
ClinGen expert clinical validity curation of 164 hearing loss gene-disease pairs
Genetics in medicine, Vol.21(10), pp.2239-2247
10/2019
DOI: 10.1038/s41436-019-0487-0
PMCID: PMC7280024
PMID: 30894701
Abstract
Proper interpretation of genomic variants is critical to successful medical decision making based on genetic testing results. A fundamental prerequisite to accurate variant interpretation is the clear understanding of the clinical validity of gene-disease relationships. The Clinical Genome Resource (ClinGen) has developed a semiquantitative framework to assign clinical validity to gene-disease relationships.
The ClinGen Hearing Loss Gene Curation Expert Panel (HL GCEP) uses this framework to perform evidence-based curations of genes present on testing panels from 17 clinical laboratories in the Genetic Testing Registry. The HL GCEP curated and reviewed 142 genes and 164 gene-disease pairs, including 105 nonsyndromic and 59 syndromic forms of hearing loss.
The final outcome included 82 Definitive (50%), 12 Strong (7%), 25 Moderate (15%), 32 Limited (20%), 10 Disputed (6%), and 3 Refuted (2%) classifications. The summary of each curation is date stamped with the HL GCEP approval, is live, and will be kept up-to-date on the ClinGen website ( https://search.clinicalgenome.org/kb/gene-validity ).
This gene curation approach serves to optimize the clinical sensitivity of genetic testing while reducing the rate of uncertain or ambiguous test results caused by the interrogation of genes with insufficient evidence of a disease link.
Details
- Title: Subtitle
- ClinGen expert clinical validity curation of 164 hearing loss gene-disease pairs
- Creators
- Marina T DiStefano - Broad InstituteSarah E Hemphill - Mass General BrighamAndrea M Oza - Boston Children's HospitalRebecca K Siegert - Broad InstituteAndrew R Grant - Broad InstituteMadeline Y Hughes - Broad InstituteBrandon J Cushman - Mass General BrighamHela Azaiez - University of IowaKevin T Booth - University of IowaAlex Chapin - ARUP LaboratoriesHatice Duzkale - Cincinnati Children's Hospital Medical CenterTatsuo Matsunaga - National Hospital OrganizationJun Shen - Harvard UniversityWenying Zhang - Cincinnati Children's Hospital Medical CenterMargaret Kenna - Boston Children's HospitalLisa A Schimmenti - Mayo ClinicMustafa Tekin - University of MiamiHeidi L Rehm - Mass General BrighamAhmad N Abou Tayoun - Al Jalila Children’s Specialty Hospital, Al Jaddaf, Dubai, United Arab EmiratesSami S Amr - Harvard UniversityClinGen Hearing Loss Clinical Domain Working Group
- Contributors
- Richard J H Smith (Contributor) - University of Iowa, Otolaryngology
- Resource Type
- Journal article
- Publication Details
- Genetics in medicine, Vol.21(10), pp.2239-2247
- DOI
- 10.1038/s41436-019-0487-0
- PMID
- 30894701
- PMCID
- PMC7280024
- ISSN
- 1098-3600
- eISSN
- 1530-0366
- Grant note
- U41 HG006834 / NHGRI NIH HHS
- Language
- English
- Date published
- 10/2019
- 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
- 9984256838902771
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