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Reactive gene curation to support interpretation and reporting of a clinical genome test for rare disease: Experience from over 1,000 cases

Current standards in clinical genetics recognize the need to establish the validity of gene-disease relationships as a first step in the interpretation of sequence variants. We describe our experience incorporating the ClinGen Gene-Disease Clinical Validity framework in our interpretation and report...

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Autores principales: Clause, Amanda R., Taylor, Julie P., Rajkumar, Revathi, Bluske, Krista, Bennett, Maren, Amendola, Laura M., Bentley, David R., Taft, Ryan J., Perry, Denise L., Coffey, Alison J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9932986/
https://www.ncbi.nlm.nih.gov/pubmed/36819666
http://dx.doi.org/10.1016/j.xgen.2023.100258
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author Clause, Amanda R.
Taylor, Julie P.
Rajkumar, Revathi
Bluske, Krista
Bennett, Maren
Amendola, Laura M.
Bentley, David R.
Taft, Ryan J.
Perry, Denise L.
Coffey, Alison J.
author_facet Clause, Amanda R.
Taylor, Julie P.
Rajkumar, Revathi
Bluske, Krista
Bennett, Maren
Amendola, Laura M.
Bentley, David R.
Taft, Ryan J.
Perry, Denise L.
Coffey, Alison J.
author_sort Clause, Amanda R.
collection PubMed
description Current standards in clinical genetics recognize the need to establish the validity of gene-disease relationships as a first step in the interpretation of sequence variants. We describe our experience incorporating the ClinGen Gene-Disease Clinical Validity framework in our interpretation and reporting workflow for a clinical genome sequencing (cGS) test for individuals with rare and undiagnosed genetic diseases. This “reactive” gene curation is completed upon identification of candidate variants during active case analysis and within the test turn-around time by focusing on the most impactful evidence and taking advantage of the broad applicability of the framework to cover a wide range of disease areas. We demonstrate that reactive gene curation can be successfully implemented in support of cGS in a clinical laboratory environment, enabling robust clinical decision making and allowing all variants to be fully and appropriately considered and their clinical significance confidently interpreted.
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spelling pubmed-99329862023-02-17 Reactive gene curation to support interpretation and reporting of a clinical genome test for rare disease: Experience from over 1,000 cases Clause, Amanda R. Taylor, Julie P. Rajkumar, Revathi Bluske, Krista Bennett, Maren Amendola, Laura M. Bentley, David R. Taft, Ryan J. Perry, Denise L. Coffey, Alison J. Cell Genom Short Article Current standards in clinical genetics recognize the need to establish the validity of gene-disease relationships as a first step in the interpretation of sequence variants. We describe our experience incorporating the ClinGen Gene-Disease Clinical Validity framework in our interpretation and reporting workflow for a clinical genome sequencing (cGS) test for individuals with rare and undiagnosed genetic diseases. This “reactive” gene curation is completed upon identification of candidate variants during active case analysis and within the test turn-around time by focusing on the most impactful evidence and taking advantage of the broad applicability of the framework to cover a wide range of disease areas. We demonstrate that reactive gene curation can be successfully implemented in support of cGS in a clinical laboratory environment, enabling robust clinical decision making and allowing all variants to be fully and appropriately considered and their clinical significance confidently interpreted. Elsevier 2023-01-31 /pmc/articles/PMC9932986/ /pubmed/36819666 http://dx.doi.org/10.1016/j.xgen.2023.100258 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Short Article
Clause, Amanda R.
Taylor, Julie P.
Rajkumar, Revathi
Bluske, Krista
Bennett, Maren
Amendola, Laura M.
Bentley, David R.
Taft, Ryan J.
Perry, Denise L.
Coffey, Alison J.
Reactive gene curation to support interpretation and reporting of a clinical genome test for rare disease: Experience from over 1,000 cases
title Reactive gene curation to support interpretation and reporting of a clinical genome test for rare disease: Experience from over 1,000 cases
title_full Reactive gene curation to support interpretation and reporting of a clinical genome test for rare disease: Experience from over 1,000 cases
title_fullStr Reactive gene curation to support interpretation and reporting of a clinical genome test for rare disease: Experience from over 1,000 cases
title_full_unstemmed Reactive gene curation to support interpretation and reporting of a clinical genome test for rare disease: Experience from over 1,000 cases
title_short Reactive gene curation to support interpretation and reporting of a clinical genome test for rare disease: Experience from over 1,000 cases
title_sort reactive gene curation to support interpretation and reporting of a clinical genome test for rare disease: experience from over 1,000 cases
topic Short Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9932986/
https://www.ncbi.nlm.nih.gov/pubmed/36819666
http://dx.doi.org/10.1016/j.xgen.2023.100258
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