Curating the Clinical Genome 2024 ePoster Gallery-Performance of REVEL Scores in PAH VCEP Variants Submitted to ClinVar

Performance of REVEL Scores in PAH VCEP Variants Submitted to ClinVar

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The document discusses the impact of applying REVEL scores and computational evidence on the interpretation of PAH missense variants. It compares the 2015 ACMG/AMP guidelines with the 2022 ClinGen SVI recommendations and highlights discrepancies in variant interpretation. By removing or adding computational evidence like PP3 and BP4, changes in clinical significance are observed for different variants. The study reviews variants with conflicting in silico evidence and assesses their impact on clinical classification. Notably, the investigation reveals that altered usage of in silico predictors can significantly affect variant interpretation. The document emphasizes the importance of following the ClinGen SVI recommendations for variant interpretation and mentions ongoing efforts to recurate PAH missense variants using the new guidelines. Overall, the study underscores the need for consistent and standardized application of computational evidence in variant interpretation.

Keywords

REVEL scores

computational evidence

PAH missense variants

ACMG/AMP guidelines

ClinGen SVI recommendations

variant interpretation

in silico evidence

clinical significance

in silico predictors

variant classification