PIK3CA N345K

c.1035T>ANM_006218.33-179203765-T-A

PI3K-AKT gain of function transversion Cancer hotspot Absent from gnomAD ClinVar: Pathogenic AlphaMissense: likely pathogenic LM

Reports 1 in LM

ISSVA entity	Allele fraction	Sources
LM	<=1.4%	PMID35373151

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

Position in PIK3CA 16 catalogued variants in this gene

Pathway and targeted therapy

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

Open and recent trials (4 in vascular / lymphatic anomalies for alpelisib)

A Trial of Targeted Therapies for Patients With Slow-Flow or Fast-Flow Vascular Malformations RECRUITING NCT05983159 · PHASE2 · WHO ICTRP
24VA022; VATCH Alpelisib for TIE2/PIK3CA Pathway VAs ACTIVE NOT RECRUITING NCT07543822 · PHASE2 · WHO ICTRP
Alpelisib in Pediatric and Adult Patients With Lymphatic Malformations Associated With a PIK3CA Mutation. RECRUITING NCT05948943 · PHASE2, PHASE3 · WHO ICTRP
A Study of Clinical Practice and Real-world Care of Patients Treated With mTOR, PI3K, and MEK Inhibitors for Extracranial Vascular Anomalies NOT YET RECRUITING NCT07767877 · WHO ICTRP

Primary sources 1

Somatic activating BRAF variants cause isolated lymphatic malformations.
Zenner K, Jensen DM, Dmyterko V, Shivaram GM, Myers CT, Paschal CR, Rudzinski ER, Pham MM, Cheng VC, Manning SC, Bly RA, Ganti S, Perkins JA, Bennett JT. · HGG Adv · 2022

Mentioned in 261 publications indexed by Europe PMC.