Publication
Title
ClinGen expert clinical validity curation of 164 hearing loss gene-disease pairs
Author
Institution/Organisation
ClinGen Hearing Loss Clinical Domain Working Group
Abstract
Purpose 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. Methods 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. Results 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). Conclusion 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.
Language
English
Source (journal)
Genetics in medicine. - Philadelphia, Pa.
Publication
Philadelphia, Pa. : 2019
ISSN
1098-3600
1530-0366
DOI
10.1038/S41436-019-0487-0
Volume/pages
21 :10 (2019) , p. 2239-2247
ISI
000488530100012
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
Project info
GENOMED - Genomics in Medicine.
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identifier
Creation 02.12.2019
Last edited 30.12.2024
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