Adaptation and validation of the ACMG/AMP variant classification framework for MYH7-associated inherited cardiomyopathies: recommendations by ClinGen’s Inherited Cardiomyopathy Expert Panel.
Full text not available from this repository.Item Type: | Article |
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Status: | Published |
Official URL: | https://doi.org/10.1038/gim.2017.218 |
Journal or Publication Title: | Genetics in Medicine |
Volume: | 20 |
Number: | 3 |
Page Range: | pp. 351-359 |
Date: | 2018 |
Divisions: | Molecular Cardiology |
Depositing User: | General Admin |
Identification Number: | 10.1038/gim.2017.218 |
ISSN: | 1098-3600 |
Date Deposited: | 03 Jan 2021 22:49 |
Abstract: | Integrating genomic sequencing in clinical care requires standardization of variant interpretation practices. The Clinical Genome Resource has established expert panels to adapt the American College of Medical Genetics and Genomics/Association for Molecular Pathology classification framework for specific genes and diseases. The Cardiomyopathy Expert Panel selected MYH7, a key contributor to inherited cardiomyopathies, as a pilot gene to develop a broadly applicable approach.MethodsExpert revisions were tested with 60 variants using a structured double review by pairs of clinical and diagnostic laboratory experts. Final consensus rules were established via iterative discussions.ResultsAdjustments represented disease-/gene-informed specifications (12) or strength adjustments of existing rules (5). Nine rules were deemed not applicable. Key specifications included quantitative frameworks for minor allele frequency thresholds, the use of segregation data, and a semiquantitative approach to counting multiple independent variant occurrences where fully controlled case-control studies are lacking. Initial inter-expert classification concordance was 93%. Internal data from participating diagnostic laboratories changed the classification of 20% of the variants (n = 12), highlighting the critical importance of data sharing.ConclusionThese adapted rules provide increased specificity for use in MYH7-associated disorders in combination with expert review and clinical judgment and serve as a stepping stone for genes and disorders with similar genetic and clinical characteristics. |
Creators: | Creators Email Kelly, Melissa A UNSPECIFIED Caleshu, Colleen UNSPECIFIED Morales, Ana UNSPECIFIED Buchan, Jillian UNSPECIFIED Wolf, Zena UNSPECIFIED Harrison, Steven M UNSPECIFIED Cook, Stuart UNSPECIFIED Dillon, Mitchell W UNSPECIFIED Garcia, John UNSPECIFIED Haverfield, Eden UNSPECIFIED Jongbloed, Jan D H UNSPECIFIED Macaya, Daniela UNSPECIFIED Manrai, Arjun UNSPECIFIED Orland, Kate UNSPECIFIED Richard, Gabriele UNSPECIFIED Spoonamore, Katherine UNSPECIFIED Thomas, Matthew UNSPECIFIED Thomson, Kate UNSPECIFIED Vincent, Lisa M UNSPECIFIED Walsh, Roddy UNSPECIFIED Watkins, Hugh UNSPECIFIED Whiffin, Nicola UNSPECIFIED Ingles, Jodie UNSPECIFIED van Tintelen, J Peter UNSPECIFIED Semsarian, Christopher UNSPECIFIED Ware, James S UNSPECIFIED Hershberger, Ray UNSPECIFIED Funke, Birgit UNSPECIFIED |
Last Modified: | 03 Jan 2021 22:49 |
URI: | https://eprints.centenary.org.au/id/eprint/518 |
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