// Evidence Grader
Claim grades, A through F
Every major genomics claim in this course gets a transparent grade — from clinically established interventions to outright misleading marketing. Use this dashboard to audit what's settled, what's preliminary, and what's hype.
A
Clinically established
B
Supported, context-specific
C
Promising, preliminary
D
Plausible, unproven
E
Popular, weak support
F
Misleading or false
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A
The ACMG/AMP 2015 criteria are the standard for germline variant classification
Universally adopted; ClinGen continues to refine gene/disease-specific specifications.
Module 03 · Variant Interpretation: ACMG, VUS, and Penetrance →A
REVEL outperforms older missense predictors at clinically relevant thresholds
ClinGen Sequence Variant Interpretation working group recalibration confirms it on independent test sets.
Module 03 · Variant Interpretation: ACMG, VUS, and Penetrance →C
AlphaMissense should be used as primary clinical evidence today
Strong benchmark performance, but ClinGen has not yet defined formal evidence-strength tiers; treat as supporting.
Module 03 · Variant Interpretation: ACMG, VUS, and Penetrance →A
Population biobank-based penetrance estimates are systematically lower than family-based estimates
Documented across BRCA1/2, LDLR, MYH7, MYBPC3, LMNA, and ATTR.
Module 03 · Variant Interpretation: ACMG, VUS, and Penetrance →E
Direct-to-consumer 'health risk' reports based on a few SNPs accurately predict individual disease risk
23andMe-style reports explain a small fraction of variance; PRS-based reports are better but still calibration-poor outside the training ancestry.
Module 03 · Variant Interpretation: ACMG, VUS, and Penetrance →