PIK3CA H1047L

c.3140A>TNM_006218.33-179234297-A-T

PI3K-AKT gain of function transversion Cancer hotspot Absent from gnomAD ClinVar: Pathogenic LM GLA CCLA

Reports 3 in LM · GLA · CCLA

ISSVA entity	Allele fraction	Sources
LM	2.47-6.91% (Brouillard 2021: 2.47-2.52%; Li 2023: 5-6.91%; Blesinger 2018 LEC line, Osborn 2015: n.r.)	PMID34112235 PMID37264205 PMID29985963 PMID25292196
GLA	18.5% (LM tissue, FFPE; GLA006)	PMID30591517
CCLA	0.15-1.25%	PMID37264205

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)

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
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

Primary sources 5

Genomic profiling informs diagnoses and treatment in vascular anomalies.
Li D, Sheppard SE, March ME, Battig MR, Surrey LF, Srinivasan AS, Matsuoka LS, Tian L, Wang F, Seiler C, Dayneka J, Borst AJ, Matos MC, Paulissen SM, Krishnamurthy G, Nriagu B, Sikder T, Casey M, Williams L, Rangu S, O'Connor N, Thomas A, Pinto E, Hou C, Nguyen K, Pellegrino da Silva R, Chehimi SN, Kao C, Biroc L, Britt AD, Queenan M, Reid JR, Napoli JA, Low DM, Vatsky S, Treat J, Smith CL, Cahill AM, Snyder KM, Adams DM, Dori Y, Hakonarson H. · Nat Med · 2023
Non-hotspot PIK3CA mutations are more frequent in CLOVES than in common or combined lymphatic malformations.
Brouillard P, Schlögel MJ, Homayun Sepehr N, Helaers R, Queisser A, Fastré E, Boutry S, Schmitz S, Clapuyt P, Hammer F, Dompmartin A, Weitz-Tuoretmaa A, Laranne J, Pasquesoone L, Vilain C, Boon LM, Vikkula M. · Orphanet J Rare Dis · 2021
Somatic activating mutations in PIK3CA cause generalized lymphatic anomaly.
Rodriguez-Laguna L, Agra N, Ibañez K, Ibañez K, Oliva-Molina G, Gordo G, Khurana N, Hominick D, Beato M, Colmenero I, Herranz G, Torres Canizalez JM, Rodríguez Pena R, Vallespín E, Martín-Arenas R, Del Pozo Á, Villaverde C, Bustamante A, Ayuso C, Lapunzina P, Lopez-Gutierrez JC, Dellinger MT, Martinez-Glez V. · J Exp Med · 2019
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
Activating PIK3CA alleles and lymphangiogenic phenotype of lymphatic endothelial cells isolated from lymphatic malformations.
Osborn AJ, Dickie P, Neilson DE, Glaser K, Lynch KA, Gupta A, Dickie BH. · Hum Mol Genet · 2015

Mentioned in 618 publications indexed by Europe PMC.