← Lymphatic Malformation Variant Atlas

CBL Y774*

c.2322T>G NM_005188.4 RAS-MAPK transversion, loss of function

Cancer hotspot Not a hotspot stop gained. Genome Nexus / cancerhotspots.org

Population · gnomAD 1.3e-5 gnomAD v4

ClinVar Not in ClinVar no exact-match submission

Protein region linker region, C-terminal to the Cbl-PTB domain Residue 774 of CBL. UniProt P22681

Position in CBL 1 catalogued

Reported in KLA

ISSVA subset	Allele fraction	Sources
KLA	4%	PMC7539180

Bars show the reported allele-fraction range on a 0 to 50 percent axis.

Pathway and targeted therapy

Driver of the RAS-MAPK pathway. Repurposed drugs already used in the clinic for this pathway: trametinib and other MEK inhibitors.

Open and recent trials (8 in vascular / lymphatic anomalies for trametinib)

Trametinib Treatment for Complicated Vascular Anomalies ACTIVE NOT RECRUITING NCT07072403 · PHASE1, PHASE2
24VA021; VATCH Trametinib for Ras/MAPK Pathway VAs ACTIVE NOT RECRUITING NCT07549646 · PHASE2
Pilot Study on Trametinib for Surgical Unruptured AVMs WITHDRAWN NCT06098872 · PHASE2
A Phase I/II Study of Trametinib and Azacitidine for Patients With Newly Diagnosed Juvenile Myelomonocytic Leukemia RECRUITING NCT05849662 · PHASE1, PHASE2
TAPUR: Testing the Use of Food and Drug Administration (FDA) Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer RECRUITING NCT02693535 · PHASE2
Pediatric Long-Term Follow-up and Rollover Study ACTIVE NOT RECRUITING NCT03975829 · PHASE4

Primary sources (1)

Kaposiform lymphangiomatosis effectively treated with MEK inhibition.
Foster JB, Li D, March ME, Sheppard SE, Adams DM, Hakonarson H, Dori Y. · EMBO Mol Med · 2020

Mentioned in 64 publications indexed by Europe PMC.

Cross-references

gnomAD · CBL ClinVar · Y774* OncoKB cBioPortal · CBL VarSome UniProt · CBL AlphaFold · CBL