2:46
5G
OmicsNex · cascade
TP53 R175H germline · daughter age 38 · Li-Fraumeni surveillance
LFS
Syndrome flagged
Toronto
Protocol activates
CONTRA
Tamoxifen + RT
TP53 R175H · separate LFS hit on case-001 family★ PEER-SIGNED ×2
VAR
TP53 c.524G>A (p.R175H) germline · ClinVar 4★ Hotspot · DNA-binding-domain · Pathogenic by ACMG/AMP (PS3 + PM5 + PP3 + PP5)
PATHO
SIG
Two signatures: @adrienne (FACMG) + @adrienne (MSMC) Cross-MSMC peer-review · classification merged 2 hours ago · COIN minted
+3 COIN
CPIC
Tamoxifen + radiotherapy contraindicated in TP53-mutant BRCA PharmGKB Tier-1A · secondary-malignancy risk · alternative regimen surfaced
CONTRA
PROT
Toronto Protocol surveillance activated for daughter Whole-body MRI annually · breast MRI from age 25 · colonoscopy from age 25 · brain MRI Q2y from 18
ACTIVE
PED
Family pedigree · 3 generations · two pathogenic hits Proband (45F, BRCA1+) · daughter (38F, TP53+) · mother d. ovary 52 · mat aunt breast 38 · mat gm breast 41 · cascade pending son (35M) + sister (47F)
G3
SCHED
Daughter's surveillance calendar · first 12 months 2026-05-20 WBM-MRI MSMC · 2026-06-15 breast MRI · 2026-08-12 colonoscopy · 2026-11-15 WBM-MRI repeat · auto-staged to MyChart + Apple Health
12mo
FED
Cascade propagates across the galaxy OncoNex tumor-board-014 updated · AnkiNex card #17 (PI3K mechanism) re-anchored to LFS · CaribChat cohort 152 flagged · CaseNex case-001 family-tree subtree extended
×4
LLAUDE0.1.0(2)
Ad
Adrienne · FACMG
cascade — daughter age 38, any LFS hit?
L
LAUDE
TP53 R175H germline on panel — hotspot, DNA-binding-domain. Combined criteria PS3 + PM5 + PP3 + PP5 → Pathogenic. Toronto Protocol surveillance opens; tamoxifen + RT contraindicated per CPIC Tier-1A.
Ad
Irman · FACMG · MSMC
co-sign — same MSMC system, second reviewer ready
L
LAUDE
Both signatures captured. cls-tp53-r175h-case-001 hash-chained. +3 COIN minted to each signer. Surfaces in case-001's family-pedigree subtree + OncoNex tumor-board-protocol-014.
Schedule the daughter's first MRI…
Ad
Two weeks later. Cascade screen on the patient's daughter, age 38.
TP53 R175H germline — a separate Li-Fraumeni hit on the same pedigree. Adrienne classifies. Irman co-signs from MSMC. Toronto Protocol surveillance activates. Tamoxifen + radiotherapy contraindicated.
SLIDE ?? / ??
Cascade · 2 weeks later · 2:46pm

The cascade activates.
Toronto Protocol on the daughter.

01
Separate hit on the same family
Daughter (38) panels positive for TP53 R175H germline — a Li-Fraumeni hotspot. Independent of the mother's BRCA1. Two pathogenic variants, one pedigree, two surveillance protocols.
02
Cross-MSMC peer-signature
Adrienne (FACMG) classifies. Irman (FACMG · MSMC) co-signs as second reviewer — same system, faster cycle. Hash-chain locks, COIN mints to both.
03
CPIC contraindication lands immediately
Tamoxifen + radiotherapy contraindicated in TP53-mutant breast cancer (PharmGKB Tier-1A). LAUDE surfaces this as the classification merges — no clinician digs for it.
04
Toronto Protocol becomes a calendar
Whole-body MRI annually · breast MRI from 25 · colonoscopy from 25. LAUDE schedules the daughter's first MRI from the cascade view. Surveillance is operational, not a PDF.
CANONIC Nexus
magic://hadleylab/OMICSNEX/cls-tp53-r175h-case-001 · Li-Fraumeni cascade
LEDGER · CLASSIFY · CASE_PEER_REVIEW_SIGNED ×2 · +6 COIN