Publications by authors named "Christine M Pak"
Article Synopsis
- - The ClinGen Actionability Working Group (AWG) created a framework to evaluate and score gene-condition pairs related to secondary findings from genome sequencing, and recently added actionability assertions to this framework.
- - The initial rubric was based on previously evaluated pairs, refined through expert feedback, and now uses a 4-point scale to determine the actionability of each gene-condition pair, generating both preliminary and consensus assertions.
- - Over 170 adult and 188 pediatric gene-condition pairs have been assessed, with the aim of improving clinical decision-making regarding the return of secondary findings from genetic testing.
Purpose: Synthesis and curation of evidence regarding the clinical actionability of secondary findings (SFs) from genome-scale sequencing are needed to support decision-making on reporting of these findings. To assess actionability of SFs in children and adolescents, the Clinical Genome Resource established the Pediatric Actionability Working Group (AWG).
Methods: The Pediatric AWG modified the framework of the existing Adult AWG, which included production of summary reports of actionability for genes and associated conditions and consensus actionability scores for specific outcome-intervention pairs.
Article Synopsis
- - Evaluating genetic variants for pathogenicity is complex due to the various types of evidence, leading to the need for standardized guidelines, which were established by ACMG and AMP in 2015.
- - A pilot study involving nine molecular diagnostic labs tested these guidelines on 99 variants, showing high agreement within labs (79%) but low agreement across labs (34%) initially.
- - After discussions and revisions of the ACMG-AMP criteria, the concordance across labs improved to 71%, highlighting the importance of collaborative review and clarity in standardizing variant interpretations for Mendelian diseases.