chr3:179218303:G>A Detail (hg38) (PIK3CA)

Information

Genome

Assembly Position
hg19 chr3:178,936,091-178,936,091 View the variant detail on this assembly version.
hg38 chr3:179,218,303-179,218,303

HGVS

Type Transcript Protein
RefSeq NM_006218.3:c.1633G>A NP_006209.2:p.Glu545Lys
Ensemble ENST00000263967.4:c.1633G>A ENST00000263967.4:p.Glu545Lys
ENST00000643187.1:c.1633G>A ENST00000643187.1:p.Glu545Lys
Summary

MGeND

Clinical significance Likely pathogenic Pathogenic
Variant entry 10
GWAS entry
Disease area statistics Show details

Frequency

JP HGVD:[No Data.]
ToMMo:[No Data.]
NCBN:[No Data.]
NCBN(Hondo):[No Data.]
NCBN(Ryukyu):[No Data.]
East asia ExAC:<0.001

Prediction

ClinVar

Clinical Significance Pathogenic Likely pathogenic
Review star
Show details
Links
Type Database ID Link
Gene MIM 171834 OMIM
HGNC 8975 HGNC
Ensembl ENSG00000121879 Ensembl
NCBI NCBI
Gene Cards Gene Cards
OncoKB OncoKB
Type Database ID Link
Variant TogoVar
COSMIC COSM763 COSMIC
MONDO
Disease area statistics
MGeND
Clinical significance Last evaluated Condition Origin Submission ID Submitter Institute Citation Comment Image
Pathogenic 2017/11/09 Endometrioid adenocarcinoma somatic MGS000017
(TMGS000052) 		Kohei Miyazono Tokyo University
Pathogenic 2018/03/22 uterine body cancer somatic MGS000017
(TMGS000052) 		Kohei Miyazono Tokyo University
Pathogenic 2018/03/22 squamous cell carcinoma somatic MGS000017
(TMGS000052) 		Kohei Miyazono Tokyo University
Pathogenic 2018/04/12 Malignant transformation of mature cystic teratoma somatic MGS000017
(TMGS000052) 		Kohei Miyazono Tokyo University
Likely pathogenic colorectal neoplasms, hereditary nonpolyposis somatic MGS000043
(TMGS000096) 		Kohei Miyazono Tokyo University
Likely pathogenic salivary gland neoplasms somatic MGS000044
(TMGS000097) 		Kohei Miyazono Tokyo University
ClinVar
Clinical significance Last evaluated Review status Condition Origin Links
Pathogenic 2012-06-24 no assertion criteria provided breast adenocarcinoma somatic Detail
Pathogenic 2012-06-24 no assertion criteria provided OVARIAN CANCER, EPITHELIAL, SOMATIC somatic Detail
Pathogenic 2012-06-24 no assertion criteria provided Carcinoma of colon somatic Detail
Pathogenic 2012-06-24 no assertion criteria provided seborrheic keratosis somatic Detail
Pathogenic 2014-10-02 no assertion criteria provided Non-small cell lung carcinoma somatic Detail
Pathogenic 2012-06-24 no assertion criteria provided Megalencephaly-capillary malformation-polymicrogyria syndrome somatic unknown Detail
not provided no assertion provided sarcoma somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided prostate adenocarcinoma somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided Squamous cell lung carcinoma somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided pancreatic adenocarcinoma somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided Squamous cell carcinoma of the head and neck somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided Papillary renal cell carcinoma type 1 somatic Detail
Pathogenic Likely pathogenic 2018-12-01 no assertion criteria provided Neoplasm of ovary somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided Carcinoma of esophagus somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided Malignant neoplasm of body of uterus somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided ovarian serous cystadenocarcinoma somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided Nasopharyngeal neoplasm somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided Neoplasm of uterine cervix somatic Detail
Pathogenic 2016-05-31 no assertion criteria provided Breast neoplasm somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided Malignant melanoma of skin somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided Papillary renal cell carcinoma, sporadic somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided Small cell lung carcinoma somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided hepatocellular carcinoma somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided gallbladder carcinoma somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided glioblastoma somatic Detail
Pathogenic 2016-05-31 no assertion criteria provided Neoplasm of the large intestine somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided lung adenocarcinoma somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided gastric adenocarcinoma somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided uterine carcinosarcoma somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided Neoplasm of brain somatic Detail
Pathogenic 2024-01-01 criteria provided, multiple submitters, no conflicts not provided somatic germline Detail
Pathogenic Likely pathogenic 2019-01-01 criteria provided, multiple submitters, no conflicts CLOVES syndrome unknown somatic Detail
Pathogenic 2023-11-01 criteria provided, multiple submitters, no conflicts PIK3CA related overgrowth syndrome somatic germline Detail
Pathogenic no assertion criteria provided somatic Detail
Pathogenic 2020-10-30 no assertion criteria provided gallbladder cancer somatic Detail
Pathogenic 2021-04-06 criteria provided, single submitter somatic Detail
Pathogenic 2021-09-30 no assertion criteria provided Cerebrofacial Vascular Metameric Syndrome (CVMS) somatic Detail
Pathogenic 2021-10-21 criteria provided, single submitter Eccrine Angiomatous Hamartoma somatic Detail
Pathogenic 2012-06-24 no assertion criteria provided Gastric cancer somatic Detail
Pathogenic 2012-06-24 no assertion criteria provided HEMIFACIAL MYOHYPERPLASIA, SOMATIC somatic Detail
Likely pathogenic 2024-03-19 no assertion criteria provided Angioosteohypertrophic syndrome somatic Detail
Likely pathogenic 2024-03-19 no assertion criteria provided Rare venous malformation somatic Detail
Likely pathogenic 2024-03-19 no assertion criteria provided Rare combined vascular malformation somatic Detail
CIViC
Disease Drug EL ET ED CS VO TR Pubmed Links
lung adenocarcinoma Gefitinib D Predictive Supports Resistance Somatic 2 16906227 Detail
Her2-receptor positive breast cancer Trastuzumab D Predictive Supports Resistance Somatic 2 18829560 Detail
cancer Apitolisib C Predictive Supports Sensitivity/Response Somatic 1 26787751 Detail
lung adenocarcinoma Erlotinib,Afatinib,Gefitinib B Predictive Supports Resistance Somatic 2 27304188 Detail
breast cancer PI3K Inhibitor GDC-0941 Bismesylate D Predictive Supports Sensitivity/Response Somatic 2 20453058 Detail
Her2-receptor positive breast cancer Trastuzumab Emtansine B Predictive Supports Sensitivity/Response Somatic 26920887 Detail
colorectal cancer Panitumumab,Cetuximab C Predictive Does Not Support Resistance Somatic 2 19223544 Detail
lung non-small cell carcinoma PI103 D Predictive Supports Sensitivity/Response Somatic 2 19513541 Detail
cervix carcinoma Pictilisib D Predictive Supports Sensitivity/Response Somatic 3 27489350 Detail
cervix carcinoma Cisplatin D Predictive Supports Resistance Somatic 3 27489350 Detail
melanoma Vemurafenib D Predictive Supports Resistance Somatic 2 24265155 Detail
colorectal cancer Panitumumab,Cetuximab C Predictive Supports Resistance Somatic 3 19223544 Detail
breast cancer Pictilisib,Akt Inhibitor MK2206 D Predictive Supports Sensitivity/Response Somatic 3 23888070 Detail
DisGeNET
Score Disease name Description Source Pubmed Links
0.120 breast adenocarcinoma NA CLINVAR Detail
0.137 Non-small cell lung carcinoma NA CLINVAR Detail
0.065 breast carcinoma We further validated the approach in breast cancer cells with mutational activat... BeFree 21775521 Detail
0.080 breast carcinoma This study proposed to investigate the relationship of PIK3CA somatic mutations,... BeFree 25027743 Detail
0.080 breast carcinoma This study proposed to investigate the relationship of PIK3CA somatic mutations,... BeFree 25027743 Detail
<0.001 Oropharyngeal disorders PIK3CA mutations were identified by Sanger sequencing in 23 of 75 (31%) HPV-posi... BeFree 24341335 Detail
0.001 cholangiocarcinoma PIK3CA missense mutations were found in one of 11 intrahepatic CCA (E545K, 9%), ... BeFree 18181165 Detail
0.131 colon carcinoma NA CLINVAR Detail
0.240 Malignant neoplasm of breast This study proposed to investigate the relationship of PIK3CA somatic mutations,... BeFree 25027743 Detail
0.241 sarcoma NA CLINVAR Detail
0.364 seborrheic keratosis NA CLINVAR Detail
0.246 Stomach Neoplasms NA CLINVAR Detail
0.036 breast carcinoma This study proposed to investigate the relationship of PIK3CA somatic mutations,... BeFree 25027743 Detail
0.360 Megalencephaly cutis marmorata telangiectatica congenita NA CLINVAR Detail
0.051 Malignant neoplasm of breast This study proposed to investigate the relationship of PIK3CA somatic mutations,... BeFree 25027743 Detail
0.104 Malignant neoplasm of breast This study proposed to investigate the relationship of PIK3CA somatic mutations,... BeFree 25027743 Detail
0.377 liver carcinoma PIK3CA missense mutations were found in one of 11 intrahepatic CCA (E545K, 9%), ... BeFree 18181165 Detail
0.304 Malignant neoplasm of breast We further validated the approach in breast cancer cells with mutational activat... BeFree 21775521 Detail
0.128 Epithelial ovarian cancer NA CLINVAR Detail
Annotation

Annotations

DescrptionSourceLinks
HCC827 cell lines harboring activated PI3K (HCC827 p110α E545K cells) were more resistant to gefitin... CIViC Evidence Detail
PI3K mutant E545K was overexpressed in the trastuzumab sensitive HER2 BT474 breast cancer cell line,... CIViC Evidence Detail
Phase 1 study with the dual PI3K/mTOR inhibitor apitolisib. 120 patients were treated at doses betwe... CIViC Evidence Detail
48 tumor samples from 41 patients with EGFR mutant lung adenocarcinoma that were resistant to tyrosi... CIViC Evidence Detail
Breast cancer cell lines with oncogenic PIK3CA mutations had an increased sensitivity to treatment w... CIViC Evidence Detail
In a phase 3 clinical trial (NCT00829166), metastatic breast cancer patients with PIK3CA mutation (n... CIViC Evidence Detail
In this study, a large cohort of metastatic colorectal cancer patients were treated with anti-epider... CIViC Evidence Detail
H460, a gefitinib-resistant NSCLC cell line harboring PIK3CA E545K (a PIK3CA activating mutation), w... CIViC Evidence Detail
CaSki cells that are heterozygous for the PIK3CA-E545K mutation are more resistant to cisplatin or c... CIViC Evidence Detail
CaSki cells that are heterozygous for the PIK3CA-E545K mutation are more resistant to cisplatin or c... CIViC Evidence Detail
An in vitro study of M229 (a human melanoma cell line) endogenously expressing wildtype PIK3CA and B... CIViC Evidence Detail
In this study, a large cohort of metastatic colorectal cancer patients were treated with anti-epider... CIViC Evidence Detail
PIK3CA E545K mutation increased sensitivity to AKT inhibitor MK-2206 and PI3K inhibitor GDC-0941 in ... CIViC Evidence Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Breast adenocarcinoma ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND OVARIAN CANCER, EPITHELIAL, SOMATIC ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Carcinoma of colon ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Seborrheic keratosis ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Non-small cell lung carcinoma ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Megalencephaly-capillary malformation-polymicrogyria... ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Sarcoma ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Prostate adenocarcinoma ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Squamous cell lung carcinoma ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Pancreatic adenocarcinoma ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Squamous cell carcinoma of the head and neck ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Papillary renal cell carcinoma type 1 ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Neoplasm of ovary ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Carcinoma of esophagus ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Malignant neoplasm of body of uterus ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Ovarian serous cystadenocarcinoma ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Transitional cell carcinoma of the bladder ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Nasopharyngeal neoplasm ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Neoplasm of uterine cervix ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Breast neoplasm ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Malignant melanoma of skin ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Papillary renal cell carcinoma, sporadic ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Small cell lung carcinoma ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Hepatocellular carcinoma ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Gallbladder carcinoma ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Glioblastoma ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Neoplasm of the large intestine ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Lung adenocarcinoma ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Gastric adenocarcinoma ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Uterine carcinosarcoma ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Brainstem glioma ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Neoplasm of brain ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND not provided ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND CLOVES syndrome ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND PIK3CA related overgrowth syndrome ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Abnormal cardiovascular system morphology ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Gallbladder cancer ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Segmental undergrowth associated with lymphatic malf... ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Cerebrofacial Vascular Metameric Syndrome (CVMS) ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Eccrine Angiomatous Hamartoma ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Gastric cancer ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND HEMIFACIAL MYOHYPERPLASIA, SOMATIC ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Angioosteohypertrophic syndrome ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Rare venous malformation ClinVar Detail
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) AND Rare combined vascular malformation ClinVar Detail
NA DisGeNET Detail
NA DisGeNET Detail
We further validated the approach in breast cancer cells with mutational activation of PIK3CA, where... DisGeNET Detail
This study proposed to investigate the relationship of PIK3CA somatic mutations, the most common act... DisGeNET Detail
This study proposed to investigate the relationship of PIK3CA somatic mutations, the most common act... DisGeNET Detail
PIK3CA mutations were identified by Sanger sequencing in 23 of 75 (31%) HPV-positive oropharyngeal c... DisGeNET Detail
PIK3CA missense mutations were found in one of 11 intrahepatic CCA (E545K, 9%), one of 23 gallbladde... DisGeNET Detail
NA DisGeNET Detail
This study proposed to investigate the relationship of PIK3CA somatic mutations, the most common act... DisGeNET Detail
NA DisGeNET Detail
NA DisGeNET Detail
NA DisGeNET Detail
This study proposed to investigate the relationship of PIK3CA somatic mutations, the most common act... DisGeNET Detail
NA DisGeNET Detail
This study proposed to investigate the relationship of PIK3CA somatic mutations, the most common act... DisGeNET Detail
This study proposed to investigate the relationship of PIK3CA somatic mutations, the most common act... DisGeNET Detail
PIK3CA missense mutations were found in one of 11 intrahepatic CCA (E545K, 9%), one of 23 gallbladde... DisGeNET Detail
We further validated the approach in breast cancer cells with mutational activation of PIK3CA, where... DisGeNET Detail
NA DisGeNET Detail

Overlapped Transcript Coordinates

Gene Transcript ID Exon Number Chromosome Start Stop Type Amino Mutation Transcript Position Links

Overlapped Transcript

Gene Transcript ID Chromosome Start Stop Links
Gene
-
dbSNP
rs104886003 dbSNP
Genome
hg38
Position
chr3:179,218,303-179,218,303
Variant Type
snv
Reference Allele
G
Alternative Allele
A
East Asian Chromosome Counts (ExAC)
8604
East Asian Allele Counts (ExAC)
0
East Asian Heterozygous Counts (ExAC)
0
East Asian Homozygous Counts (ExAC)
0
East Asian Allele Frequency (ExAC)
0.0
Chromosome Counts in All Race (ExAC)
119906
Allele Counts in All Race (ExAC)
1
Heterozygous Counts in All Race (ExAC)
1
Homozygous Counts in All Race (ExAC)
0
Allele Frequency in All Race (ExAC)
8.339866228545694E-6
Variant (CIViC) (CIViC Variant)
E545K
Transcript 1 (CIViC Variant)
ENST00000263967.3
Variant URL (CIViC Variant)
https://civic.genome.wustl.edu/links/variants/104
Summary (CIViC Variant)
PIK3CA E545K/E542K are the second most recurrent PIK3CA mutations in breast cancer, and are highly recurrent mutations in many other cancer types. E545K, and possibly the other mutations in the E545 region, may present patients with a poorer prognosis than patients with either patients with other PIK3CA variant or wild-type PIK3CA. There is also data to suggest that E545/542 mutations may confer resistance to EGFR inhibitors like cetuximab. While very prevalent, targeted therapies for variants in PIK3CA are still in early clinical trial phases.
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