Variant reclassification and recontact research: A scoping review

Area of Science:

• Clinical Genetics
• Genomic Medicine
• Bioinformatics

Background:

• Accurate variant interpretation and communication are critical in clinical genetics.
• Lack of standardized guidelines for variant reclassification and patient notification creates practice challenges.
• Existing research on variant reclassification and recontact needs systematic characterization.

Purpose of the Study:

• To systematically review and characterize the scope and outcomes of research on variant reclassification and recontact in medical genetics (2013-2023).
• To summarize findings on variant reclassification frequencies, outcomes, and stakeholder perspectives.
• To identify research gaps and inform the development of standardized practices.

Main Methods:

• Systematic literature review of variant reclassification and recontact research.
• Screening of 159 nonduplicate records, with 54 research articles included for analysis.
• Categorization of studies by approach: active reclassification, passive reclassification, stakeholder surveys, qualitative interviews, and data reanalysis.

Main Results:

• Active and passive reclassification approaches yielded frequencies of 31% and 20%, respectively, significantly higher than ClinVar (<0.1%-6.4%).
• Studies reported on variant reclassification frequencies, outcomes, and diverse stakeholder perspectives on reclassification and recontact.
• Consensus exists on the need for standardization, but opinions differ on implementation strategies.

Conclusions:

• Active reclassification studies demonstrate the potential for improved variant classification through routine reinterpretation and reanalysis.
• Identified research gaps include understanding non-genetics providers' practices and opinions.
• Further research and deliberative processes are needed to achieve consensus on standardized variant reclassification and recontact guidelines.