Curating the Clinical Genome 2024 ePoster Gallery-Pushing the Limit(ed)s Modifications to a Gene-Disease Validity Framework for Common Diseases and the Impact on Clinical Utility of Genetic Testing

Pushing the Limit(ed)s Modifications to a Gene-Disease Validity Framework for Common Diseases and the Impact on Clinical Utility of Genetic Testing

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The document discusses the impact of modifications to a Gene-Disease Validity (GDV) framework on the clinical utility of genetic testing for common diseases, specifically hereditary cancer predisposition. The advancements in next-generation sequencing have led to increased gene discovery, emphasizing the importance of standardized GDV curation for multigene panel testing design and variant assessment. The dynamic nature of GDV curation is crucial for interpreting genetic variation accurately.<br /><br />Over a 7-year period, the GDV framework was revised to provide discrete scoring rules for evaluating gene-disease associations, leading to changes in classifications based on new evidence. The study found that while genes with definitive gene-disease relationships remained stable, most genes with strong and moderate relationships shifted categories. Genes associated with breast cancer were more likely to be downgraded, highlighting the need for continuous reassessment.<br /><br />The research underscores the limited clinical utility of genes with limited evidence on hereditary cancer predisposition panels and emphasizes the importance of considering phenotype frequency and heterogeneity in GDV curation to prevent premature characterizations in common diseases. The findings suggest a critical need for ongoing review and adaptation of GDV frameworks to ensure the accuracy and clinical relevance of genetic testing for hereditary cancer predisposition.

Keywords

Gene-Disease Validity

GDV framework

clinical utility

genetic testing

hereditary cancer predisposition

next-generation sequencing

multigene panel testing

variant assessment

gene discovery

GDV curation