VCV000045466.15 - ClinVar

NM_006218.4(PIK3CA):c.1637A>G (p.Gln546Arg)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(18)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

Oncogenicity

The aggregate oncogenicity classification for this variant for one or more tumor types, using the ClinGen/CGC/VICC terminology. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(1)

Stars represent the aggregate review status, or the level of review supporting the aggregate oncogenicity classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Oncogenic

criteria provided, single submitter

Variant Details

Identifiers

NM_006218.4(PIK3CA):c.1637A>G (p.Gln546Arg)

Variation ID: 45466 Accession: VCV000045466.15

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 3q26.32 3: 179218307 (GRCh38) [ NCBI UCSC ] 3: 178936095 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Feb 24, 2015	May 12, 2024	Aug 9, 2023
Somatic - Oncogenicity	Aug 11, 2024	Aug 11, 2024	Jul 31, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_006218.4:c.1637A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_006209.2:p.Gln546Arg	missense
NC_000003.12:g.179218307A>G
NC_000003.11:g.178936095A>G
NG_012113.2:g.74785A>G
LRG_310:g.74785A>G
LRG_310t1:c.1637A>G
	P42336:p.Gln546Arg

... more HGVS ... less HGVS

Protein change

Q546R

Other names

Canonical SPDI

NC_000003.12:179218306:A:G

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA136371 UniProtKB: P42336#VAR_026182 dbSNP: rs397517201 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
PIK3CA		No evidence available	No evidence available	GRCh38 GRCh37	1303	1337

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Ovarian neoplasm	Pathogenic (2)	criteria provided, single submitter	Aug 10, 2010	RCV000038672.9
Neoplasm of uterine cervix	Likely pathogenic (1)	no assertion criteria provided	May 31, 2016	RCV000417964.2
Uterine carcinosarcoma	Likely pathogenic (1)	no assertion criteria provided	May 31, 2016	RCV000427826.2
Malignant neoplasm of body of uterus	Likely pathogenic (1)	no assertion criteria provided	May 31, 2016	RCV000423116.2
Transitional cell carcinoma of the bladder	Likely pathogenic (1)	no assertion criteria provided	May 31, 2016	RCV000424486.2
Breast neoplasm	Pathogenic (1)	no assertion criteria provided	May 31, 2016	RCV000439651.2
Prostate adenocarcinoma	Likely pathogenic (1)	no assertion criteria provided	May 31, 2016	RCV000434246.2
Medulloblastoma	Likely pathogenic (1)	no assertion criteria provided	May 31, 2016	RCV000442332.2
Squamous cell carcinoma of the head and neck	Likely pathogenic (1)	no assertion criteria provided	May 31, 2016	RCV000434598.2
Neoplasm of the large intestine	Pathogenic (1)	no assertion criteria provided	May 31, 2016	RCV000422863.2
Gastric adenocarcinoma	Likely pathogenic (1)	no assertion criteria provided	May 31, 2016	RCV000435640.2
Malignant melanoma of skin	Likely pathogenic (1)	no assertion criteria provided	May 31, 2016	RCV000440779.2
Neoplasm of brain	Likely pathogenic (1)	no assertion criteria provided	May 31, 2016	RCV000443308.2
Glioblastoma	Likely pathogenic (1)	no assertion criteria provided	May 31, 2016	RCV000433168.2
Abnormal cardiovascular system morphology	Pathogenic (1)	no assertion criteria provided	-	RCV001327965.2
not provided	Pathogenic (1)	criteria provided, single submitter	Feb 4, 2021	RCV002254273.3
PIK3CA related overgrowth syndrome	Pathogenic (1)	criteria provided, single submitter	Aug 9, 2023	RCV003458193.1
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Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Aug 10, 2010)	criteria provided, single submitter (LMM Criteria) Method: clinical testing	Ovarian Cancer Affected status: not provided Allele origin: somatic	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000062350.3 First in ClinVar: May 03, 2013 Last updated: Feb 24, 2015	Publications: PubMed (4) PubMed: 20177704‚ 16353168‚ 19671852‚ 18371219 Number of individuals with the variant: 1
Pathogenic (Aug 09, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	PIK3CA-related overgrowth syndrome Affected status: yes Allele origin: somatic	Clinical Genomics Laboratory, Washington University in St. Louis Accession: SCV004176941.1 First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023	Comment: A PIK3CA c.1637A>G (p.Gln546Arg) variant was identified at an allelic fraction consistent with somatic origin. The PIK3CA c.1637A>G (p.Gln546Arg) variant has been reported in multiple … (more) A PIK3CA c.1637A>G (p.Gln546Arg) variant was identified at an allelic fraction consistent with somatic origin. The PIK3CA c.1637A>G (p.Gln546Arg) variant has been reported in multiple individuals affected with PROS disorders, including patients with lymphatic malformations (Kuentz P et al., PMID: 28151489; Piacitelli AM et al., PMID: 30063105; Parker VER et al., PMID: 30270358; McNulty SN et al., PMID: 31585106; Brouillard P et al., PMID: 34112235). This variant has been reported in the ClinVar database as pathogenic/likely pathogenic by multiple submitters (ClinVar Variation ID: 54633). It has also been reported in multiple cases in the cancer database COSMIC (Genomic Mutation ID: COSV55876869). The PIK3CA c.1637A>G (p.Gln546Arg) variant is absent from the general population (gnomAD v.2.1.1), indicating it is not a common variant. Computational predictors suggest that this variant may have a deleterious impact on the structure and/or function of the PIK3CA-encoded protein. Functional studies show p.Gln546Arg to be activating, as demonstrated by increased transformation ability in multiple cell lines (Dogruluk T et al., PMID: 26627007; Ng PK et al., PMID: 29533785). Multiple variants in the same codon, p.Gln546Glu, p.Gln546His, p.Gln546Leu, p.Gln546Lys, and p.Gln546Pro, have been reported and are considered pathogenic (ClinVar Variation IDs: 13654, 376491, 375899, 13657, 375898). Based on an internally-developed protocol informed by the ACMG/AMP guidelines (Richards S et al., PMID: 25741868) and gene-specific practices from the ClinGen Criteria Specification Registry, the PIK3CA c.1637A>G (p.Gln546Arg) variant is classified as pathogenic. (less)
Pathogenic (Feb 04, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: yes Allele origin: somatic	Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital Accession: SCV002525570.2 First in ClinVar: Jun 11, 2022 Last updated: May 12, 2024	Comment: This variant has previously been reported in multiple unrelated individuals with PIK3CA-related segmental overgrowth syndrome (PMID: 25681199, PMID: 31585106). Phenotypic information was limited in the … (more) This variant has previously been reported in multiple unrelated individuals with PIK3CA-related segmental overgrowth syndrome (PMID: 25681199, PMID: 31585106). Phenotypic information was limited in the majority of cases, but one individual had a clinical diagnosis of Fibro-Adipose Vascular Anomaly (FAVA) (PMID: 25681199). PIK3CA variants associated with PROS, including this patient's alteration, overlap those reported as oncogenic variants found in multiple tumor types (cBioPortal and NCI's Genomic Data Commons cancer databases). The p.Gln546Arg replaces the glutamine at codon 546 with arginine within the helical domain of the PIK3CA protein (UniProt P42336). Experimental studies have demonstrated that the p.Gln546Arg variant causes overactivation of the PI3K/AKT/mTOR pathway and increased proliferation in vitro (PMID: 26627007). (less) Observation 1: Number of individuals with the variant: 1 Clinical Features: Overgrowth (present) , Capillary malformation (present) , Congenital macrodactylia (present) Observation 2: Number of individuals with the variant: 1 Clinical Features: Venous malformation (present) Observation 3: Number of individuals with the variant: 1 Observation 4: Number of individuals with the variant: 1
Pathogenic (May 31, 2016)	no assertion criteria provided Method: literature only	Breast neoplasm (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000504079.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (9) PubMed: 15647370‚ 18725974‚ 22162589‚ 26619011‚ 15805248‚ 18676830‚ 15254419‚ 22162582‚ 20453058 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000263967:c.1637A>G
Likely pathogenic (May 31, 2016)	no assertion criteria provided Method: literature only	Glioblastoma (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000504081.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (1) PubMed: 26619011 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000263967:c.1637A>G
Pathogenic (May 31, 2016)	no assertion criteria provided Method: literature only	Neoplasm of the large intestine (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000504080.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (11) PubMed: 22162582‚ 19366826‚ 20453058‚ 20619739‚ 26619011‚ 22162589‚ 15016963‚ 15647370‚ 15254419‚ 19903786‚ 18725974 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000263967:c.1637A>G
Likely pathogenic (May 31, 2016)	no assertion criteria provided Method: literature only	Neoplasm of brain (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000504085.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (1) PubMed: 26619011 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000263967:c.1637A>G
Likely pathogenic (May 31, 2016)	no assertion criteria provided Method: literature only	Malignant melanoma of skin (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000504082.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (1) PubMed: 26619011 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000263967:c.1637A>G
Likely pathogenic (May 31, 2016)	no assertion criteria provided Method: literature only	Malignant neoplasm of body of uterus (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000504083.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (1) PubMed: 26619011 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000263967:c.1637A>G
Likely pathogenic (May 31, 2016)	no assertion criteria provided Method: literature only	Prostate adenocarcinoma (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000504084.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (1) PubMed: 26619011 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000263967:c.1637A>G
Likely pathogenic (May 31, 2016)	no assertion criteria provided Method: literature only	None (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000504087.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (1) PubMed: 26619011 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000263967:c.1637A>G
Likely pathogenic (May 31, 2016)	no assertion criteria provided Method: literature only	Uterine carcinosarcoma (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000504086.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (1) PubMed: 26619011 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000263967:c.1637A>G
Likely pathogenic (May 31, 2016)	no assertion criteria provided Method: literature only	Medulloblastoma (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000504088.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (1) PubMed: 26619011 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000263967:c.1637A>G
Likely pathogenic (May 31, 2016)	no assertion criteria provided Method: literature only	Transitional cell carcinoma of the bladder (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000504089.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (1) PubMed: 26619011 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000263967:c.1637A>G
Likely pathogenic (May 31, 2016)	no assertion criteria provided Method: literature only	Neoplasm of uterine cervix (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000504091.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (1) PubMed: 26619011 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000263967:c.1637A>G
Likely pathogenic (May 31, 2016)	no assertion criteria provided Method: literature only	Gastric adenocarcinoma (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000504090.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (1) PubMed: 26619011 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000263967:c.1637A>G
Pathogenic (-)	no assertion criteria provided Method: provider interpretation	Abnormal cardiovascular system morphology Affected status: yes Allele origin: somatic	MAGI's Lab - Research, MAGI Group Accession: SCV001437641.1 First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021
Likely pathogenic (Dec 01, 2018)	no assertion criteria provided Method: research	Ovarian neoplasm Affected status: yes Allele origin: somatic	German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne Accession: SCV000923960.1 First in ClinVar: Jun 17, 2019 Last updated: Jun 17, 2019
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Comment:

A PIK3CA c.1637A>G (p.Gln546Arg) variant was identified at an allelic fraction consistent with somatic origin. The PIK3CA c.1637A>G (p.Gln546Arg) variant has been reported in multiple individuals affected with PROS disorders, including patients with lymphatic malformations (Kuentz P et al., PMID: 28151489; Piacitelli AM et al., PMID: 30063105; Parker VER et al., PMID: 30270358; McNulty SN et al., PMID: 31585106; Brouillard P et al., PMID: 34112235). This variant has been reported in the ClinVar database as pathogenic/likely pathogenic by multiple submitters (ClinVar Variation ID: 54633). It has also been reported in multiple cases in the cancer database COSMIC (Genomic Mutation ID: COSV55876869). The PIK3CA c.1637A>G (p.Gln546Arg) variant is absent from the general population (gnomAD v.2.1.1), indicating it is not a common variant. Computational predictors suggest that this variant may have a deleterious impact on the structure and/or function of the PIK3CA-encoded protein. Functional studies show p.Gln546Arg to be activating, as demonstrated by increased transformation ability in multiple cell lines (Dogruluk T et al., PMID: 26627007; Ng PK et al., PMID: 29533785). Multiple variants in the same codon, p.Gln546Glu, p.Gln546His, p.Gln546Leu, p.Gln546Lys, and p.Gln546Pro, have been reported and are considered pathogenic (ClinVar Variation IDs: 13654, 376491, 375899, 13657, 375898). Based on an internally-developed protocol informed by the ACMG/AMP guidelines (Richards S et al., PMID: 25741868) and gene-specific practices from the ClinGen Criteria Specification Registry, the PIK3CA c.1637A>G (p.Gln546Arg) variant is classified as pathogenic.

Comment:

This variant has previously been reported in multiple unrelated individuals with PIK3CA-related segmental overgrowth syndrome (PMID: 25681199, PMID: 31585106). Phenotypic information was limited in the majority of cases, but one individual had a clinical diagnosis of Fibro-Adipose Vascular Anomaly (FAVA) (PMID: 25681199). PIK3CA variants associated with PROS, including this patient's alteration, overlap those reported as oncogenic variants found in multiple tumor types (cBioPortal and NCI's Genomic Data Commons cancer databases). The p.Gln546Arg replaces the glutamine at codon 546 with arginine within the helical domain of the PIK3CA protein (UniProt P42336). Experimental studies have demonstrated that the p.Gln546Arg variant causes overactivation of the PI3K/AKT/mTOR pathway and increased proliferation in vitro (PMID: 26627007).

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.	Chang MT	Nature biotechnology	2016	PMID: 26619011
Phase I, dose-escalation study of BKM120, an oral pan-Class I PI3K inhibitor, in patients with advanced solid tumors.	Bendell JC	Journal of clinical oncology : official journal of the American Society of Clinical Oncology	2012	PMID: 22162589
Phosphatidylinositide-3-kinase inhibitors: addressing questions of isoform selectivity and pharmacodynamic/predictive biomarkers in early clinical trials.	Clarke PA	Journal of clinical oncology : official journal of the American Society of Clinical Oncology	2012	PMID: 22162582
Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis.	De Roock W	The Lancet. Oncology	2010	PMID: 20619739
Predictive biomarkers of sensitivity to the phosphatidylinositol 3' kinase inhibitor GDC-0941 in breast cancer preclinical models.	O'Brien C	Clinical cancer research : an official journal of the American Association for Cancer Research	2010	PMID: 20453058
Alterations in p53, BRCA1, ATM, PIK3CA, and HER2 genes and their effect in modifying clinicopathological characteristics and overall survival of Bulgarian patients with breast cancer.	Bozhanov SS	Journal of cancer research and clinical oncology	2010	PMID: 20177704
PIK3CA mutations predict local recurrences in rectal cancer patients.	He Y	Clinical cancer research : an official journal of the American Association for Cancer Research	2009	PMID: 19903786
PIK3CA mutation associates with improved outcome in breast cancer.	Kalinsky K	Clinical cancer research : an official journal of the American Association for Cancer Research	2009	PMID: 19671852
PIK3CA mutations are not a major determinant of resistance to the epidermal growth factor receptor inhibitor cetuximab in metastatic colorectal cancer.	Prenen H	Clinical cancer research : an official journal of the American Association for Cancer Research	2009	PMID: 19366826
Breast tumor cells with PI3K mutation or HER2 amplification are selectively addicted to Akt signaling.	She QB	PloS one	2008	PMID: 18725974
An integrative genomic and proteomic analysis of PIK3CA, PTEN, and AKT mutations in breast cancer.	Stemke-Hale K	Cancer research	2008	PMID: 18676830
PIK3CA-activating mutations and chemotherapy sensitivity in stage II-III breast cancer.	Liedtke C	Breast cancer research : BCR	2008	PMID: 18371219
PIK3CA mutation and histological type in breast carcinoma: high frequency of mutations in lobular carcinoma.	Buttitta F	The Journal of pathology	2006	PMID: 16353168
PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma.	Saal LH	Cancer research	2005	PMID: 15805248
Phosphatidylinositol 3-kinase mutations identified in human cancer are oncogenic.	Kang S	Proceedings of the National Academy of Sciences of the United States of America	2005	PMID: 15647370
The PIK3CA gene is mutated with high frequency in human breast cancers.	Bachman KE	Cancer biology & therapy	2004	PMID: 15254419
High frequency of mutations of the PIK3CA gene in human cancers.	Samuels Y	Science (New York, N.Y.)	2004	PMID: 15016963
http://docm.genome.wustl.edu/variants/ENST00000263967:c.1637A>G	-	-	-	-
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Conditions - Somatic

Tumor type Help The tumor type for this variant-condition (RCV) record in ClinVar.	Clinical impact (# of submissions) Help The aggregate somatic clinical impact for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to the aggregate somatic clinical impact is shown in parentheses. The corresponding review status for the RCV record is indicated by stars. Read our rules for calculating the review status.	Oncogenicity Help The aggregate oncogenicity classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to the aggregate oncogenicity classification is shown in parentheses. The corresponding review status for the RCV record is indicated by stars. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the tumor type.	Variation/condition record Help The most recent date that a submitter evaluated this variant for the tumor type.
Neoplasm		Oncogenic criteria provided, single submitter	Jul 31, 2024	RCV004668762.1

Submissions - Somatic

Oncogenicity Help The submitted oncogenicity classification for each SCV record. (Last evaluated)	Review Status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Tumor type Help The tumor type for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the somatic clinical impact, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.

Oncogenic

(Jul 31, 2024)

(ClinGen/CGC/VICC Guidelines for Oncogenicity, 2022)

Method: clinical testing

Neoplasm

Affected status: unknown

Allele origin: somatic

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Accession: SCV005094534.1
First In ClinVar: Aug 11, 2024
Last updated: Aug 11, 2024

Comment:

Citations for somatic classification of this variant

There are no citations for somatic classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs397517201 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Aug 18, 2024

ClinVar Genomic variation as it relates to human health

NM_006218.4(PIK3CA):c.1637A>G (p.Gln546Arg)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Conditions - Somatic

Submissions - Somatic

Citations for somatic classification of this variant

Text-mined citations for rs397517201 ...