Variant evidence review
How to review PVS1 evidence for a germline variant
PVS1 concerns predicted loss-of-function evidence in a gene where loss of function is an established disease mechanism. Variant type alone is not enough: transcript relevance, predicted consequence, location and gene-specific guidance can change whether and at what strength the criterion is appropriate.
Agent question
Does this variant return PVS1 evidence, at what strength, and what source-linked facts support it?
Read the returned evidence before the label
Resolve the public GRCh38 variant first. Report the normalized identity, returned consequence, applied criterion and strength, and source provenance. If PVS1 is absent, do not infer it from a predicted truncating consequence.
Professional review questions
A qualified reviewer should assess whether loss of function is a relevant disease mechanism and whether the transcript and affected region are biologically relevant. Gene-specific ClinGen specifications take precedence when available.
- Is the variant identity unambiguous?
- Is loss of function an established mechanism for the gene-disease relationship?
- Is the affected transcript biologically relevant?
- Could transcript context or rescue mechanisms alter the predicted effect?
- Does gene-specific guidance modify the general framework?
Public references
Clinical and data boundary
Folklore Clinical Variant Interpretation MCP is published by Helena Bioinformatics. It accepts public variant-level queries only, not patient, phenotype, family, segregation or private case data. Its results are automated decision support for qualified professional review, not a diagnosis or treatment recommendation.