ClinGen expert clinical validity curation of 164 hearing loss gene–disease pairs

on behalf of the ClinGen Hearing Loss Clinical Domain Working Group

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
JournalGenetics in Medicine
DOIs
Publication statusPublished - 2019 Jan 1

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Hearing Loss
Genome
Genes
Genetic Testing
Registries

Keywords

  • ClinGen
  • deafness
  • gene curation
  • genetic diagnosis
  • hearing loss

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

ClinGen expert clinical validity curation of 164 hearing loss gene–disease pairs. / on behalf of the ClinGen Hearing Loss Clinical Domain Working Group.

In: Genetics in Medicine, 01.01.2019.

Research output: Contribution to journalArticle

on behalf of the ClinGen Hearing Loss Clinical Domain Working Group. / ClinGen expert clinical validity curation of 164 hearing loss gene–disease pairs. In: Genetics in Medicine. 2019.
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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.",
keywords = "ClinGen, deafness, gene curation, genetic diagnosis, hearing loss",
author = "{on behalf of the ClinGen Hearing Loss Clinical Domain Working Group} and DiStefano, {Marina T.} and Hemphill, {Sarah E.} and Oza, {Andrea M.} and Siegert, {Rebecca K.} and Grant, {Andrew R.} and Hughes, {Madeline Y.} and Cushman, {Brandon J.} and Hela Azaiez and Booth, {Kevin T.} and Alex Chapin and Hatice Duzkale and Tatsuo Matsunaga and Jun Shen and Wenying Zhang and Margaret Kenna and Schimmenti, {Lisa A.} and Mustafa Tekin and Rehm, {Heidi L.} and Tayoun, {Ahmad N.Abou} and Amr, {Sami S.} and Sonia Abdelhak and John Alexander and Karen Avraham and Neha Bhatia and Donglin Bai and Nicole Boczek and Zippora Brownstein and Rachel Burt and Yasmin Bylstra and {del Castillo}, Ignacio and Choi, {Byung Yoon} and Lilian Downie and Thomas Friedman and Anne Giersch and Jasmine Goh and John Greinwald and Griffith, {Andrew J.} and Amy Hernandez and Jeffrey Holt and Makoto Hosoya and Ying, {Lim Jiin} and Kanika Jain and Kim, {Un Kyung} and Hannie Kremer and Ian Krantz and Suzanne Leal and Morag Lewis and Liu, {Xue Zhong} and Wendy Low and Yu Lu",
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AU - Oza, Andrea M.

AU - Siegert, Rebecca K.

AU - Grant, Andrew R.

AU - Hughes, Madeline Y.

AU - Cushman, Brandon J.

AU - Azaiez, Hela

AU - Booth, Kevin T.

AU - Chapin, Alex

AU - Duzkale, Hatice

AU - Matsunaga, Tatsuo

AU - Shen, Jun

AU - Zhang, Wenying

AU - Kenna, Margaret

AU - Schimmenti, Lisa A.

AU - Tekin, Mustafa

AU - Rehm, Heidi L.

AU - Tayoun, Ahmad N.Abou

AU - Amr, Sami S.

AU - Abdelhak, Sonia

AU - Alexander, John

AU - Avraham, Karen

AU - Bhatia, Neha

AU - Bai, Donglin

AU - Boczek, Nicole

AU - Brownstein, Zippora

AU - Burt, Rachel

AU - Bylstra, Yasmin

AU - del Castillo, Ignacio

AU - Choi, Byung Yoon

AU - Downie, Lilian

AU - Friedman, Thomas

AU - Giersch, Anne

AU - Goh, Jasmine

AU - Greinwald, John

AU - Griffith, Andrew J.

AU - Hernandez, Amy

AU - Holt, Jeffrey

AU - Hosoya, Makoto

AU - Ying, Lim Jiin

AU - Jain, Kanika

AU - Kim, Un Kyung

AU - Kremer, Hannie

AU - Krantz, Ian

AU - Leal, Suzanne

AU - Lewis, Morag

AU - Liu, Xue Zhong

AU - Low, Wendy

AU - Lu, Yu

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N2 - 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.

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