Curating the Clinical Genome 2024 ePoster Gallery-Recuration of Hearing Loss Associated-genes Demonstrate Significant Change in Gene-disease Validity Over Time

Recuration of Hearing Loss Associated-genes Demonstrate Significant Change in Gene-disease Validity Over Time

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The document discusses the recuration of hearing loss-associated genes and their changing gene-disease validity over time by the Hearing Loss GCEP. Various institutions, including The Broad Institute and Mass General Brigham Personalized Medicine, are involved in this effort. The recuration process involves classifying gene-disease pairs based on clinical validity, with some genes associated with nonsyndromic hearing loss while others with syndromic hearing loss. The ClinGen framework guides the recuration process, requiring genes with disputed, limited, moderate, and strong relationships to be recurred every 2-3 years. Changes in gene classifications, such as upgrades or downgrades, have been observed based on new evidence. Specific examples of genes like MSRB3 and WFS1 illustrate how recuration can impact genetic scores and classifications. Overall, the recuration of 35 gene-disease pairs between 2020-2023 revealed reclassifications based on new evidence or scoring adjustments in the SOP, highlighting the dynamic nature of gene-disease relationships. Additionally, the document emphasizes the ongoing nature of gene recuration and the importance of expert-reviewed classifications to ensure accurate gene-disease validity information is available.

Keywords

Hearing Loss GCEP

Broad Institute

Mass General Brigham Personalized Medicine

gene-disease validity

nonsyndromic hearing loss

syndromic hearing loss

ClinGen framework

recuration process

MSRB3

WFS1