PIK3CA C420R

c.1258T>C NM_006218.3 PI3K-AKT transition, gain of function

Cancer hotspot Recurrent missense variant. COSMIC COSV55874020

Population · gnomAD Not observed Absent from the population database, consistent with a somatic, non-inherited driver.

ClinVar Pathogenic VCV000031945

Protein region C2 PI3K-type Residue 420 of PIK3CA. UniProt P42336

AlphaMissense likely pathogenic Pathogenicity score 1.00. Computational prediction, not clinical evidence.

Position in PIK3CA 14 catalogued

Reported in LM

ISSVA subset	Allele fraction	Sources
LM	LEC line	PMC6037383 PMC4498659

Pathway and targeted therapy

Driver of the PI3K-AKT pathway. Repurposed drugs already used in the clinic for this pathway: alpelisib (PI3Kα inhibitor), sirolimus (mTOR inhibitor).

Open and recent trials (3 in vascular / lymphatic anomalies for alpelisib)

Alpelisib in Pediatric and Adult Patients With Lymphatic Malformations Associated With a PIK3CA Mutation. RECRUITING NCT05948943 · PHASE2, PHASE3
A Trial of Targeted Therapies for Patients With Slow-Flow or Fast-Flow Vascular Malformations RECRUITING NCT05983159 · PHASE2
24VA022; VATCH Alpelisib for TIE2/PIK3CA Pathway VAs ACTIVE NOT RECRUITING NCT07543822 · PHASE2

Primary sources (2)

PIK3CA mutations are specifically localized to lymphatic endothelial cells of lymphatic malformations.
Blesinger H, Kaulfuß S, Aung T, Schwoch S, Prantl L, Rößler J, Wilting J, Becker J. · PLoS One · 2018
Lymphatic and other vascular malformative/overgrowth disorders are caused by somatic mutations in PIK3CA.
Luks VL, Kamitaki N, Vivero MP, Uller W, Rab R, Bovée JV, Rialon KL, Guevara CJ, Alomari AI, Greene AK, Fishman SJ, Kozakewich HP, Maclellan RA, Mulliken JB, Rahbar R, Spencer SA, Trenor CC, Upton J, Zurakowski D, Perkins JA, Kirsh A, Bennett JT, Dobyns WB, Kurek KC, Warman ML, McCarroll SA, Murillo R. · J Pediatr · 2015

Mentioned in 289 publications indexed by Europe PMC.

Cross-references

COSMIC COSV55874020 rs121913272 gnomAD · PIK3CA ClinVar · C420R OncoKB cBioPortal · PIK3CA VarSome UniProt · PIK3CA AlphaFold · PIK3CA