- Roughly one-third of symptomatic genetic tests end with a VUS, impacting patient care.
- SVCv4 updates the ACMG-AMP framework and makes “likely benign” easier to reach.
- New VUS subclasses (Low, Mid, High) refine uncertainty and guide clinical follow-up.
- SVCv4 is a joint effort led by ACMG, AMP, CAP, and ClinGen.
- Data sharing via ClinVar, public repositories, and gnomAD v5/v6 is essential for reclassification.
- Machine-learning tools (e.g., SpliceAI, Pangolin, PromoterAI) enhance variant impact prediction.
- Scalable functional assays help move variants from uncertain to classified.
Streamlining VUS Classification in Clinical Genomics
Conexiant
November 14, 2025
