OnCo
ideasIdea

Test every possible mutation in every cancer gene so no result is 'uncertain'

Many people get a genetic result of uncertain significance, which cannot be acted on. Lab methods now let us test every possible variant in a gene in advance.

Saturation genome editing has classified nearly all BRCA1 single-nucleotide variants, and similar maps exist for parts of other genes. Propose a philanthropy-funded consortium to produce functional maps for the roughly 30 actionable hereditary cancer genes and submit them to ClinVar.

Hypothesis
Complete functional maps resolve at least 80% of current variants of uncertain significance in hereditary cancer genes within five years.
Rationale
VUS rates of 20-40% in non-European populations undermine testing, and functional evidence is now accepted by ACMG classification frameworks.
What would test it
Fund five genes per year and track VUS reclassification rates in clinical laboratories.
Maturity
preclinical evidence
Who has to act
philanthropy
Cost to try
Medium ($1M to $50M)
Years to first evidence
4
Bottlenecks it attacks

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