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https://doi.org/10.1038/gim.2017.218
Title: | Adaptation and validation of the ACMG/AMP variant classification framework for MYH7-associated inherited cardiomyopathies: Recommendations by ClinGen's Inherited Cardiomyopathy Expert Panel | Authors: | Kelly, M.A Caleshu, C Morales, A |
Keywords: | myosin heavy chain cardiac myosin MYH7 protein, human myosin heavy chain adult Article cardiomyopathy conceptual framework congestive cardiomyopathy controlled study disease classification gene gene frequency genetic screening genetic variability human hypertrophic cardiomyopathy laboratory diagnosis MYH7 gene pathogenesis pilot study restrictive cardiomyopathy retrospective study allele cardiomyopathy clinical decision making expert witness genetic disorder genetic variation genetics phenotype procedures reproducibility standards Alleles Cardiac Myosins Cardiomyopathies Clinical Decision-Making Expert Testimony Gene Frequency Genetic Diseases, Inborn Genetic Testing Genetic Variation Humans Myosin Heavy Chains Phenotype Reproducibility of Results |
Issue Date: | 2018 | Publisher: | Nature Publishing Group | Citation: | Kelly, M.A, Caleshu, C, Morales, A (2018). Adaptation and validation of the ACMG/AMP variant classification framework for MYH7-associated inherited cardiomyopathies: Recommendations by ClinGen's Inherited Cardiomyopathy Expert Panel. Genetics in Medicine 20 (3) : 351-359. ScholarBank@NUS Repository. https://doi.org/10.1038/gim.2017.218 | Rights: | Attribution 4.0 International | Abstract: | Purpose: 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. Methods: Expert 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. Results: Adjustments 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. Conclusion: These 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. © 2018 American College of Medical Genetics and Genomics. | Source Title: | Genetics in Medicine | URI: | https://scholarbank.nus.edu.sg/handle/10635/179048 | ISSN: | 10983600 | DOI: | 10.1038/gim.2017.218 | Rights: | Attribution 4.0 International |
Appears in Collections: | Elements Staff Publications |
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