ClinVar Genomic variation as it relates to human health
NM_006218.4(PIK3CA):c.3140A>G (p.His1047Arg)
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_006218.4(PIK3CA):c.3140A>G (p.His1047Arg)
Variation ID: 13652 Accession: VCV000013652.76
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 3q26.32 3: 179234297 (GRCh38) [ NCBI UCSC ] 3: 178952085 (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 Oct 1, 2013 May 12, 2024 Feb 11, 2022 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_006218.4:c.3140A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_006209.2:p.His1047Arg missense NC_000003.12:g.179234297A>G NC_000003.11:g.178952085A>G NG_012113.2:g.90775A>G LRG_310:g.90775A>G LRG_310t1:c.3140A>G P42336:p.His1047Arg - Protein change
- H1047R
- Other names
- NM_006218.4(PIK3CA):c.3140A>G
- COSM775
- Canonical SPDI
- NC_000003.12:179234296:A:G
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- effect on protein activity Variation Ontology [VariO:0053]
- gain_of_function_variant Sequence Ontology [SO:0002053]
-
Global minor allele
frequency (GMAF) HelpThe 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.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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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 | ||
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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. |
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PIK3CA | No evidence available | No evidence available |
GRCh38 GRCh37 |
1239 | 1273 |
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. |
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Pathogenic (1) |
no assertion criteria provided
|
Jun 24, 2012 | RCV000014624.16 | |
Pathogenic/Likely pathogenic (2) |
no assertion criteria provided
|
May 31, 2016 | RCV000014626.17 | |
Pathogenic (3) |
no assertion criteria provided
|
Oct 2, 2014 | RCV000014627.22 | |
Pathogenic (1) |
no assertion criteria provided
|
Jun 24, 2012 | RCV000014628.17 | |
Pathogenic (1) |
no assertion criteria provided
|
Jun 24, 2012 | RCV000014623.17 | |
Pathogenic (5) |
criteria provided, multiple submitters, no conflicts
|
Nov 11, 2019 | RCV000024621.24 | |
Pathogenic (1) |
no assertion criteria provided
|
Jun 24, 2012 | RCV000014622.17 | |
Pathogenic (3) |
no assertion criteria provided
|
Dec 1, 2018 | RCV000154516.15 | |
Pathogenic (2) |
criteria provided, single submitter
|
Apr 19, 2019 | RCV000201231.10 | |
Likely pathogenic (1) |
no assertion criteria provided
|
May 31, 2016 | RCV000425956.9 | |
Likely pathogenic (1) |
no assertion criteria provided
|
May 31, 2016 | RCV000430589.9 | |
Likely pathogenic (1) |
no assertion criteria provided
|
May 31, 2016 | RCV000432543.9 | |
Likely pathogenic (1) |
no assertion criteria provided
|
May 31, 2016 | RCV000433127.9 | |
Likely pathogenic (1) |
no assertion criteria provided
|
May 31, 2016 | RCV000420562.9 | |
Pathogenic (1) |
no assertion criteria provided
|
May 31, 2016 | RCV000436234.9 | |
Likely pathogenic (1) |
no assertion criteria provided
|
May 31, 2016 | RCV000437287.9 | |
Likely pathogenic (1) |
no assertion criteria provided
|
May 31, 2016 | RCV000426498.9 | |
Likely pathogenic (1) |
no assertion criteria provided
|
May 31, 2016 | RCV000426614.9 | |
Likely pathogenic (1) |
no assertion criteria provided
|
May 31, 2016 | RCV000442736.9 | |
Pathogenic (1) |
no assertion criteria provided
|
May 31, 2016 | RCV000437153.9 | |
Likely pathogenic (1) |
no assertion criteria provided
|
May 31, 2016 | RCV000442731.9 | |
Likely pathogenic (1) |
no assertion criteria provided
|
May 31, 2016 | RCV000421855.9 | |
Likely pathogenic (1) |
no assertion criteria provided
|
May 31, 2016 | RCV000422442.9 | |
Likely pathogenic (1) |
no assertion criteria provided
|
May 31, 2016 | RCV000428372.9 | |
Likely pathogenic (1) |
no assertion criteria provided
|
May 31, 2016 | RCV000431232.9 | |
Likely pathogenic (1) |
no assertion criteria provided
|
May 31, 2016 | RCV000437782.9 | |
Likely pathogenic (1) |
no assertion criteria provided
|
Jul 14, 2015 | RCV000438435.9 | |
Likely pathogenic (1) |
no assertion criteria provided
|
May 31, 2016 | RCV000443546.9 | |
Pathogenic (1) |
no assertion criteria provided
|
Jun 24, 2012 | RCV000709691.11 | |
Pathogenic (1) |
criteria provided, single submitter
|
- | RCV000487449.10 | |
Likely pathogenic (1) |
no assertion criteria provided
|
May 31, 2016 | RCV000419938.9 | |
Likely pathogenic (1) |
no assertion criteria provided
|
May 31, 2016 | RCV000432506.9 | |
Likely pathogenic (1) |
no assertion criteria provided
|
May 31, 2016 | RCV000442164.9 | |
Pathogenic (1) |
no assertion criteria provided
|
Jun 24, 2012 | RCV001728091.9 | |
Pathogenic (1) |
criteria provided, single submitter
|
Oct 1, 2021 | RCV001729349.9 | |
Pathogenic (1) |
no assertion criteria provided
|
Sep 30, 2021 | RCV001730472.9 | |
Pathogenic (1) |
criteria provided, single submitter
|
- | RCV001526648.9 | |
Pathogenic (1) |
reviewed by expert panel
|
Feb 11, 2022 | RCV001836707.10 | |
Pathogenic (1) |
criteria provided, single submitter
|
Apr 6, 2021 | RCV001705589.9 | |
Pathogenic (1) |
criteria provided, single submitter
|
Apr 6, 2021 | RCV001705590.9 | |
Pathogenic (1) |
no assertion criteria provided
|
Jun 24, 2012 | RCV002508124.8 | |
Pathogenic/Likely pathogenic (6) |
criteria provided, multiple submitters, no conflicts
|
Aug 3, 2022 | RCV001092442.31 | |
Likely pathogenic (1) |
no assertion criteria provided
|
Mar 19, 2024 | RCV004527291.1 | |
Pathogenic (1) |
no assertion criteria provided
|
- | RCV003128082.8 | |
Pathogenic (1) |
criteria provided, single submitter
|
Mar 23, 2023 | RCV003325939.6 | |
Pathogenic (1) |
no assertion criteria provided
|
Apr 30, 2019 | RCV001255686.9 | |
Pathogenic (1) |
no assertion criteria provided
|
- | RCV001327968.9 | |
Pathogenic (1) |
criteria provided, single submitter
|
Feb 12, 2021 | RCV001807727.9 | |
Likely pathogenic (1) |
no assertion criteria provided
|
Mar 19, 2024 | RCV004527290.1 | |
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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. |
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Pathogenic
(Feb 11, 2022)
|
reviewed by expert panel
Method: curation
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Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
ClinGen Brain Malformations Variant Curation Expert Panel
Accession: SCV001949970.2
First in ClinVar: Oct 02, 2021 Last updated: Feb 20, 2022 |
Comment:
The c.3140A>G (NM_006218.4) variant in PIK3CA is a missense variant predicted to cause substitution of (p.His1047Arg). This variant is present in one individual in gnomAD … (more)
The c.3140A>G (NM_006218.4) variant in PIK3CA is a missense variant predicted to cause substitution of (p.His1047Arg). This variant is present in one individual in gnomAD v2.1.1 (PM2_Supporting). The prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls (PS4_VS; PMIDs: 27191687, 28328134, 25292196, 22729222, 25424831, 465 entries in COSMIC, Segmental overgrowth or vascular malformation of a limb or region of the body, present in patient derived cell lines). 60 independent Ba/F3 and 57 independent MCF10A experiments showed this variant has a proliferative effect indicating that this variant impacts protein function (PMID:29533785 ) (PS3_Moderate). This variant resides within the kinase domain of PIK3CA that is defined as a critical functional domain by the ClinGen BMEP (PMIDs: 26637981, 24459181, 27631024) (PM1_Supporting). PIK3CA, in which the variant was identified, is defined by the ClinGen Brain Malformations Expert Panel as a gene that has a low rate of benign missense variation and where pathogenic missense variants are a common mechanism of disease (PP2). Testing of unaffected and affected tissue show variable allelic fractions consistent with a post-zygotic event (PS2_Moderate; PMID: 25424831). In summary, this variant meets the criteria to be classified as Pathogenic for mosaic autosomal dominant overgrowth with or without cerebral malformations due to abnormalities in MTOR-pathway genes based on the ACMG/AMP criteria applied, as specified by the ClinGen Brain Malformations Expert Panel: PM2_P, PS4_VS, PS3_M, PM1_P, PP2, PS2_M; 15 points (VCEP specifications version 1; Approved: 1/31/2021) (less)
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Pathogenic
(Apr 19, 2019)
|
criteria provided, single submitter
Method: clinical testing
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PIK3CA related overgrowth spectrum
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Biesecker Lab Rare Disease, National Institutes of Health
Accession: SCV000898478.1
First in ClinVar: Apr 28, 2019 Last updated: Apr 28, 2019 |
Clinical Features:
overgrowth (present)
Sex: male
|
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Pathogenic
(Nov 11, 2019)
|
criteria provided, single submitter
Method: clinical testing
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CLOVES syndrome
Affected status: yes
Allele origin:
de novo
|
Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV001428754.1
First in ClinVar: Aug 16, 2020 Last updated: Aug 16, 2020 |
Number of individuals with the variant: 1
|
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Pathogenic
(-)
|
criteria provided, single submitter
Method: clinical testing
|
Congenital macrodactylia
Affected status: yes
Allele origin:
somatic
|
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne
Accession: SCV001737079.1
First in ClinVar: Jun 19, 2021 Last updated: Jun 19, 2021 |
|
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Pathogenic
(Oct 01, 2021)
|
criteria provided, single submitter
Method: clinical testing
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CLAPO syndrome
Affected status: yes
Allele origin:
unknown
|
Laboratory of Medical Genetics, National & Kapodistrian University of Athens
Accession: SCV001976965.1
First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021 |
Comment:
PS3, PM1, PM2, PM5, PP2, PP3, PP4, PP5
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Pathogenic
(Feb 12, 2021)
|
criteria provided, single submitter
Method: clinical testing
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Megalencephaly-capillary malformation-polymicrogyria syndrome
Affected status: no
Allele origin:
somatic
|
Centogene AG - the Rare Disease Company
Accession: SCV002059601.1
First in ClinVar: Jan 15, 2022 Last updated: Jan 15, 2022 |
|
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Pathogenic
(Jun 01, 2021)
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criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001248958.21
First in ClinVar: May 12, 2020 Last updated: May 12, 2024 |
Number of individuals with the variant: 2
|
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Pathogenic
(-)
|
criteria provided, single submitter
Method: clinical testing
|
Rosette-forming glioneuronal tumor
Affected status: yes
Allele origin:
somatic
|
Donald Williams Parsons Laboratory, Baylor College of Medicine
Additional submitter:
Sharon E. Plon Laboratory, Baylor College of Medicine
Study: CSER-BASIC3
Accession: SCV000292259.2 First in ClinVar: Apr 28, 2017 Last updated: Apr 28, 2017
Comment:
The c.3140A>G missense mutation (p.H1047R) identified in exon 21 of PIK3CA is the most frequently-observed PIK3CA hotspot alteration in human cancers , including high grade … (more)
The c.3140A>G missense mutation (p.H1047R) identified in exon 21 of PIK3CA is the most frequently-observed PIK3CA hotspot alteration in human cancers , including high grade gliomas and glioneuronal tumors (Ellezam et al. 2012), and has also been demonstrated to result in constitutive activation of the PI3K/AKT/mTOR pathway (Bader et al. 2005, Engelman 2009, Thorpe et al. 2015, Wu et al. 2014) (less)
|
Clinical Features:
Rosette-forming glioneuronal tumor (present)
Age: 10-19 years
Sex: female
Ethnicity/Population group: African American
Tissue: frozen tumor sample : Rosette-forming glioneuronal tumor of the fourth ventricle
|
|
Pathogenic
(-)
|
criteria provided, single submitter
Method: clinical testing
|
CLOVES syndrome
Affected status: yes
Allele origin:
unknown
|
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne
Study: Clinvar_gadteam_Clinical_exome_analysis_3
Accession: SCV000803841.1 First in ClinVar: Apr 21, 2017 Last updated: Apr 21, 2017 |
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Pathogenic
(Oct 23, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
(Autosomal unknown)
Affected status: yes
Allele origin:
germline
|
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001446687.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Clinical Features:
Overgrowth (present) , Congenital macrodactylia (present)
Sex: female
|
|
Pathogenic
(Apr 06, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Segmental undergrowth associated with lymphatic malformation
Affected status: yes
Allele origin:
somatic
|
Institute of Medical and Molecular Genetics, Hospital Universitario La Paz
Accession: SCV001934209.1
First in ClinVar: Sep 25, 2021 Last updated: Sep 25, 2021 |
Number of individuals with the variant: 2
Clinical Features:
Limb undergrowth (present) , Lymphangioma (present)
|
|
Pathogenic
(Apr 06, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Segmental undergrowth associated with mainly venous malformation with capillary component
Affected status: yes
Allele origin:
somatic
|
Institute of Medical and Molecular Genetics, Hospital Universitario La Paz
Accession: SCV001934211.1
First in ClinVar: Sep 25, 2021 Last updated: Sep 25, 2021 |
Number of individuals with the variant: 1
Clinical Features:
Limb undergrowth (present) , Venous malformation (present) , Capillary malformation (present)
|
|
Pathogenic
(Aug 05, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Not provided
Affected status: yes
Allele origin:
germline
|
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center
Accession: SCV002061476.2
First in ClinVar: Jan 22, 2022 Last updated: Feb 11, 2022 |
Comment:
PS4, PS3, PM2
|
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Pathogenic
(Sep 20, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
somatic
|
Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital
Accession: SCV002525705.1
First in ClinVar: Jun 11, 2022 Last updated: Jun 11, 2022 |
Comment:
This variant substitutes the histidine with arginine at position 1047 within the PIK3CA kinase domain. This is a recurrent pathogenic variant. Several unrelated individuals with … (more)
This variant substitutes the histidine with arginine at position 1047 within the PIK3CA kinase domain. This is a recurrent pathogenic variant. Several unrelated individuals with PIK3CA-related segmental overgrowth syndrome due to the somatic activating PIK3CA p.His1047Arg variant have previously been reported (PMID: 25681199, PMID: 26637981, PMID: 24903541, PMID: 30180809, PMID: 28328134 and others). (less)
Observation 1:
Number of individuals with the variant: 1
Clinical Features:
Abnormal lymphatic vessel morphology (present)
Observation 2:
Number of individuals with the variant: 1
Clinical Features:
Abnormal lymphatic vessel morphology (present)
Observation 3:
Number of individuals with the variant: 1
Clinical Features:
Abnormal lymphatic vessel morphology (present)
Observation 4:
Number of individuals with the variant: 1
Clinical Features:
Abnormal lymphatic vessel morphology (present)
Observation 5:
Number of individuals with the variant: 1
Clinical Features:
Abnormal lymphatic vessel morphology (present)
Observation 6:
Number of individuals with the variant: 1
Clinical Features:
Abnormal lymphatic vessel morphology (present)
Observation 7:
Number of individuals with the variant: 1
Clinical Features:
Abnormal lymphatic vessel morphology (present) , Overgrowth (present)
Observation 8:
Number of individuals with the variant: 1
Clinical Features:
Venous malformation (present)
Observation 9:
Number of individuals with the variant: 1
Clinical Features:
Neoplasm (present) , Vascular skin abnormality (present) , Hemangioma (present)
Observation 10:
Number of individuals with the variant: 1
Clinical Features:
Abnormal lymphatic vessel morphology (present)
Observation 11:
Number of individuals with the variant: 1
Clinical Features:
Abnormal lymphatic vessel morphology (present)
Observation 12:
Number of individuals with the variant: 1
Clinical Features:
Congenital macrodactylia (present) , Macrodactyly of finger (present)
Observation 13:
Number of individuals with the variant: 1
Observation 14:
Number of individuals with the variant: 1
Observation 15:
Number of individuals with the variant: 1
Observation 16:
Number of individuals with the variant: 1
Observation 17:
Number of individuals with the variant: 1
Observation 18:
Number of individuals with the variant: 1
Clinical Features:
Abnormal lymphatic vessel morphology (present)
|
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Pathogenic
(Aug 03, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV002559314.2
First in ClinVar: Aug 15, 2022 Last updated: Mar 04, 2023 |
Comment:
Reported as a somatic variant in various tumor samples (Campbell et al., 2004; Li et al., 2005); Published functional studies demonstrate increased lipid kinase activity … (more)
Reported as a somatic variant in various tumor samples (Campbell et al., 2004; Li et al., 2005); Published functional studies demonstrate increased lipid kinase activity and transforming activities, and a mouse model with this variant demonstrated increased body weight, increased organ size, and severe metabolic defects (Ikenoue et al., 2005; Kinross et al., 2015); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 16322209, 15289301, 15016963, 25599672, 23100325, 25550458, 15930273, 16432179, 19805105, 21708979, 15520168, 15784156, 27631024, 24903541, 22658544, 32770747, 34568242, 34075207) (less)
|
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Pathogenic
(Mar 23, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Klippel-Trenaunay-like-Syndrome
Affected status: yes
Allele origin:
somatic
|
Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust
Accession: SCV003853395.1
First in ClinVar: Sep 09, 2023 Last updated: Sep 09, 2023 |
|
|
Likely pathogenic
(Nov 03, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: not provided
Allele origin:
germline
|
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Accession: SCV002009609.3
First in ClinVar: Nov 06, 2021 Last updated: Jul 16, 2023 |
|
|
Pathogenic
(Aug 05, 2010)
|
no assertion criteria provided
Method: clinical testing
|
Ovarian Cancer
Affected status: not provided
Allele origin:
somatic
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000204187.1
First in ClinVar: Jan 31, 2015 Last updated: Jan 31, 2015 |
Number of individuals with the variant: 1
|
|
Pathogenic
(Apr 01, 2015)
|
no assertion criteria provided
Method: clinical testing
|
PIK3CA Related Overgrowth Spectrum
Affected status: yes
Allele origin:
somatic
|
Clinical Genomics Laboratory, Washington University in St. Louis
Accession: SCV000255984.2
First in ClinVar: Oct 22, 2015 Last updated: Oct 07, 2023 |
Observation 1:
Indication for testing: Lipoma
Tissue: FFPE
Observation 2:
Indication for testing: Polydactyly; Syndactyly; Other specified congenital abnormalities
Tissue: FFPE
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Ovarian serous cystadenocarcinoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000504107.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Pathogenic
(Oct 02, 2014)
|
no assertion criteria provided
Method: literature only
|
Non-small cell lung carcinoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000504111.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Brainstem glioma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000504112.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
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: SCV000504113.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
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: SCV000504108.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
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: SCV000504109.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
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: SCV000504114.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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Likely pathogenic
(May 31, 2016)
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no assertion criteria provided
Method: literature only
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Malignant neoplasm of body of uterus
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
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Database of Curated Mutations (DoCM)
Accession: SCV000504115.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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Pathogenic
(Dec 01, 2018)
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no assertion criteria provided
Method: research
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Neoplasm of ovary
Affected status: yes
Allele origin:
somatic
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German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne
Accession: SCV000923968.1
First in ClinVar: Jun 17, 2019 Last updated: Jun 17, 2019 |
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Pathogenic
(Jun 24, 2012)
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no assertion criteria provided
Method: literature only
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HEPATOCELLULAR CARCINOMA, SOMATIC
Affected status: not provided
Allele origin:
somatic
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OMIM
Accession: SCV000034881.6
First in ClinVar: Apr 04, 2013 Last updated: Oct 08, 2021 |
Comment on evidence:
Colorectal Cancer In a relatively high frequency of colorectal cancers (114500), Samuels et al. (2004) identified a his1047-to-arg (H1047R) mutation in the PIK3CA gene; in … (more)
Colorectal Cancer In a relatively high frequency of colorectal cancers (114500), Samuels et al. (2004) identified a his1047-to-arg (H1047R) mutation in the PIK3CA gene; in vitro studies showed that the H1047R mutant has increased lipid kinase activity. Breast Cancer In 5 breast tumors (114480), 7 epithelial ovarian tumors (167000), and 1 colorectal tumor from a series of 284 primary human tumors, Campbell et al. (2004) identified the H1047R mutation, which is caused by a 3140A-G transition in exon 20. Lee et al. (2005) identified a somatic H1047R mutation in 21 breast cancer tumors, 4 gastric cancer (137215) tumors, 1 hepatocellular carcinoma (114550), and 1 nonsmall cell lung cancer (211980). CLOVE Syndrome In a 2-year-old boy and an unrelated 1-year-old girl with congenital lipomatous overgrowth, vascular malformations, and epidermal nevi (CLOVE syndrome; 612918), Kurek et al. (2012) identified somatic mosaicism for the H1047R mutation in affected tissues from multiple embryonic lineages, with a mutant allele frequency ranging from 16 to 23%. Kurek et al. (2012) also stated that they had identified somatic mosaicism for H1047R in 3 patients who had been diagnosed with Klippel-Trenaunay-Weber syndrome (149000), an overgrowth syndrome with features overlapping those of CLOVE syndrome. Lindhurst et al. (2012) sequenced the PIK3CA gene in 10 individuals with an 'unclassified' syndrome of congenital progressive segmental overgrowth of fibrous and adipose tissue and bone and identified a somatic H1047R variant in 7 affected individuals, with mutation burdens ranging from less than 1% to 35% in affected tissues and fibroblast cultures. The features of the 'unclassified' syndrome were consistent with CLOVE syndrome. Seborrheic Keratosis Hafner et al. (2007) identified a heterozygous somatic H1047R mutation in a seborrheic keratosis lesion (182000). The authors emphasized that this is a benign lesion and noted that the same mutation had been observed in cancerous lesions. Macrodactyly Rios et al. (2013) identified the H1047R mutation in affected tissue from an individual (patient 6) with macrodactyly (155500). Immunochemistry showed increased staining in macrodactyly cells from patient 6 compared to control cells, indicating greater levels of ser473-phosphorylated AKT (164730) through increased activation of the PI3K-AKT cell signaling axis. Cerebral Cavernous Malformations 4 In samples of cerebral cavernous malformations-4 (CCM4; 619538) from 10 unrelated patients with sporadic occurrence of the disease, Peyre et al. (2021) identified a somatic H1047R mutation in the PIK3CA gene. The mutation was found by targeted DNA sequencing. PIK3CA-mutant CCMs showed increased phosphorylation of myosin light chain and activation of the PI3K-AKT-mTOR pathway, consistent with an activating mutation. Variant Function Using in situ genetic lineage tracing and limiting dilution transplantation, Koren et al. (2015) elucidated the potential of PIK3CA(H1047R) to induce multipotency during tumorigenesis in the mammary gland. The authors showed that expression of PIK3CA(H1047R) in lineage-committed basal Lgr5 (606667)-positive and luminal keratin-8 (KRT8; 148060)-positive cells of the adult mouse mammary gland evokes cell dedifferentiation into a multipotent stem-like state, suggesting this to be a mechanism involved in the formation of heterogeneous, multilineage mammary tumors. Moreover, Koren et al. (2015) showed that the tumor cell of origin influences the frequency of malignant mammary tumors. Koren et al. (2015) concluded that their results defined a key effect of PIK3CA(H1047R) on mammary cell fate in the preneoplastic mammary gland and showed that the cell of origin of PIK3CA(H1047R) tumors dictates their malignancy, thus revealing a mechanism underlying tumor heterogeneity and aggressiveness. Van Keymeulen et al. (2015) found that oncogenic PIK3CA(H1047R) mutant expression at physiologic levels in basal cells using keratin (K)5 (148040)-CreER(T2) mice induced the formation of luminal estrogen receptor (ER; 133430)-positive/progesterone receptor (PR; 607311)-positive tumors, while its expression in luminal cells using K8-CReER(T2) mice gave rise to luminal ER+PR+ tumors or basal-like ER-PR- tumors. Concomitant deletion of p53 (191170) and expression of Pik3ca(H1047R) accelerated tumor development and induced more aggressive mammary tumors. Interestingly, expression of Pik3ca(H1047R) in unipotent basal cells gave rise to luminal-like cells, while its expression in unipotent luminal cells gave rise to basal-like cells before progressing into invasive tumors. Transcriptional profiling of cells that underwent cell fate transition upon Pik3ca(H1047R) expression in unipotent progenitors demonstrated a profound oncogene-induced reprogramming of these newly formed cells and identified gene signatures characteristic of the different cell fate switches that occur upon Pik3ca(H1047R) expression in basal and luminal cells. Van Keymeulen et al. (2015) concluded that oncogenic Pik3ca(H1047R) activates a multipotent genetic program in normally lineage-restricted populations at the early stage of tumor initiation, setting the stage for future intratumoral heterogeneity. (less)
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Pathogenic
(Jun 24, 2012)
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no assertion criteria provided
Method: literature only
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NONSMALL CELL LUNG CANCER, SOMATIC
Affected status: not provided
Allele origin:
somatic
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OMIM
Accession: SCV000034882.6
First in ClinVar: Apr 04, 2013 Last updated: Oct 08, 2021 |
Comment on evidence:
Colorectal Cancer In a relatively high frequency of colorectal cancers (114500), Samuels et al. (2004) identified a his1047-to-arg (H1047R) mutation in the PIK3CA gene; in … (more)
Colorectal Cancer In a relatively high frequency of colorectal cancers (114500), Samuels et al. (2004) identified a his1047-to-arg (H1047R) mutation in the PIK3CA gene; in vitro studies showed that the H1047R mutant has increased lipid kinase activity. Breast Cancer In 5 breast tumors (114480), 7 epithelial ovarian tumors (167000), and 1 colorectal tumor from a series of 284 primary human tumors, Campbell et al. (2004) identified the H1047R mutation, which is caused by a 3140A-G transition in exon 20. Lee et al. (2005) identified a somatic H1047R mutation in 21 breast cancer tumors, 4 gastric cancer (137215) tumors, 1 hepatocellular carcinoma (114550), and 1 nonsmall cell lung cancer (211980). CLOVE Syndrome In a 2-year-old boy and an unrelated 1-year-old girl with congenital lipomatous overgrowth, vascular malformations, and epidermal nevi (CLOVE syndrome; 612918), Kurek et al. (2012) identified somatic mosaicism for the H1047R mutation in affected tissues from multiple embryonic lineages, with a mutant allele frequency ranging from 16 to 23%. Kurek et al. (2012) also stated that they had identified somatic mosaicism for H1047R in 3 patients who had been diagnosed with Klippel-Trenaunay-Weber syndrome (149000), an overgrowth syndrome with features overlapping those of CLOVE syndrome. Lindhurst et al. (2012) sequenced the PIK3CA gene in 10 individuals with an 'unclassified' syndrome of congenital progressive segmental overgrowth of fibrous and adipose tissue and bone and identified a somatic H1047R variant in 7 affected individuals, with mutation burdens ranging from less than 1% to 35% in affected tissues and fibroblast cultures. The features of the 'unclassified' syndrome were consistent with CLOVE syndrome. Seborrheic Keratosis Hafner et al. (2007) identified a heterozygous somatic H1047R mutation in a seborrheic keratosis lesion (182000). The authors emphasized that this is a benign lesion and noted that the same mutation had been observed in cancerous lesions. Macrodactyly Rios et al. (2013) identified the H1047R mutation in affected tissue from an individual (patient 6) with macrodactyly (155500). Immunochemistry showed increased staining in macrodactyly cells from patient 6 compared to control cells, indicating greater levels of ser473-phosphorylated AKT (164730) through increased activation of the PI3K-AKT cell signaling axis. Cerebral Cavernous Malformations 4 In samples of cerebral cavernous malformations-4 (CCM4; 619538) from 10 unrelated patients with sporadic occurrence of the disease, Peyre et al. (2021) identified a somatic H1047R mutation in the PIK3CA gene. The mutation was found by targeted DNA sequencing. PIK3CA-mutant CCMs showed increased phosphorylation of myosin light chain and activation of the PI3K-AKT-mTOR pathway, consistent with an activating mutation. Variant Function Using in situ genetic lineage tracing and limiting dilution transplantation, Koren et al. (2015) elucidated the potential of PIK3CA(H1047R) to induce multipotency during tumorigenesis in the mammary gland. The authors showed that expression of PIK3CA(H1047R) in lineage-committed basal Lgr5 (606667)-positive and luminal keratin-8 (KRT8; 148060)-positive cells of the adult mouse mammary gland evokes cell dedifferentiation into a multipotent stem-like state, suggesting this to be a mechanism involved in the formation of heterogeneous, multilineage mammary tumors. Moreover, Koren et al. (2015) showed that the tumor cell of origin influences the frequency of malignant mammary tumors. Koren et al. (2015) concluded that their results defined a key effect of PIK3CA(H1047R) on mammary cell fate in the preneoplastic mammary gland and showed that the cell of origin of PIK3CA(H1047R) tumors dictates their malignancy, thus revealing a mechanism underlying tumor heterogeneity and aggressiveness. Van Keymeulen et al. (2015) found that oncogenic PIK3CA(H1047R) mutant expression at physiologic levels in basal cells using keratin (K)5 (148040)-CreER(T2) mice induced the formation of luminal estrogen receptor (ER; 133430)-positive/progesterone receptor (PR; 607311)-positive tumors, while its expression in luminal cells using K8-CReER(T2) mice gave rise to luminal ER+PR+ tumors or basal-like ER-PR- tumors. Concomitant deletion of p53 (191170) and expression of Pik3ca(H1047R) accelerated tumor development and induced more aggressive mammary tumors. Interestingly, expression of Pik3ca(H1047R) in unipotent basal cells gave rise to luminal-like cells, while its expression in unipotent luminal cells gave rise to basal-like cells before progressing into invasive tumors. Transcriptional profiling of cells that underwent cell fate transition upon Pik3ca(H1047R) expression in unipotent progenitors demonstrated a profound oncogene-induced reprogramming of these newly formed cells and identified gene signatures characteristic of the different cell fate switches that occur upon Pik3ca(H1047R) expression in basal and luminal cells. Van Keymeulen et al. (2015) concluded that oncogenic Pik3ca(H1047R) activates a multipotent genetic program in normally lineage-restricted populations at the early stage of tumor initiation, setting the stage for future intratumoral heterogeneity. (less)
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Pathogenic
(Jun 24, 2012)
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no assertion criteria provided
Method: literature only
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BREAST CANCER, SOMATIC
Affected status: not provided
Allele origin:
somatic
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OMIM
Accession: SCV000034877.6
First in ClinVar: Apr 04, 2013 Last updated: Oct 08, 2021 |
Comment on evidence:
Colorectal Cancer In a relatively high frequency of colorectal cancers (114500), Samuels et al. (2004) identified a his1047-to-arg (H1047R) mutation in the PIK3CA gene; in … (more)
Colorectal Cancer In a relatively high frequency of colorectal cancers (114500), Samuels et al. (2004) identified a his1047-to-arg (H1047R) mutation in the PIK3CA gene; in vitro studies showed that the H1047R mutant has increased lipid kinase activity. Breast Cancer In 5 breast tumors (114480), 7 epithelial ovarian tumors (167000), and 1 colorectal tumor from a series of 284 primary human tumors, Campbell et al. (2004) identified the H1047R mutation, which is caused by a 3140A-G transition in exon 20. Lee et al. (2005) identified a somatic H1047R mutation in 21 breast cancer tumors, 4 gastric cancer (137215) tumors, 1 hepatocellular carcinoma (114550), and 1 nonsmall cell lung cancer (211980). CLOVE Syndrome In a 2-year-old boy and an unrelated 1-year-old girl with congenital lipomatous overgrowth, vascular malformations, and epidermal nevi (CLOVE syndrome; 612918), Kurek et al. (2012) identified somatic mosaicism for the H1047R mutation in affected tissues from multiple embryonic lineages, with a mutant allele frequency ranging from 16 to 23%. Kurek et al. (2012) also stated that they had identified somatic mosaicism for H1047R in 3 patients who had been diagnosed with Klippel-Trenaunay-Weber syndrome (149000), an overgrowth syndrome with features overlapping those of CLOVE syndrome. Lindhurst et al. (2012) sequenced the PIK3CA gene in 10 individuals with an 'unclassified' syndrome of congenital progressive segmental overgrowth of fibrous and adipose tissue and bone and identified a somatic H1047R variant in 7 affected individuals, with mutation burdens ranging from less than 1% to 35% in affected tissues and fibroblast cultures. The features of the 'unclassified' syndrome were consistent with CLOVE syndrome. Seborrheic Keratosis Hafner et al. (2007) identified a heterozygous somatic H1047R mutation in a seborrheic keratosis lesion (182000). The authors emphasized that this is a benign lesion and noted that the same mutation had been observed in cancerous lesions. Macrodactyly Rios et al. (2013) identified the H1047R mutation in affected tissue from an individual (patient 6) with macrodactyly (155500). Immunochemistry showed increased staining in macrodactyly cells from patient 6 compared to control cells, indicating greater levels of ser473-phosphorylated AKT (164730) through increased activation of the PI3K-AKT cell signaling axis. Cerebral Cavernous Malformations 4 In samples of cerebral cavernous malformations-4 (CCM4; 619538) from 10 unrelated patients with sporadic occurrence of the disease, Peyre et al. (2021) identified a somatic H1047R mutation in the PIK3CA gene. The mutation was found by targeted DNA sequencing. PIK3CA-mutant CCMs showed increased phosphorylation of myosin light chain and activation of the PI3K-AKT-mTOR pathway, consistent with an activating mutation. Variant Function Using in situ genetic lineage tracing and limiting dilution transplantation, Koren et al. (2015) elucidated the potential of PIK3CA(H1047R) to induce multipotency during tumorigenesis in the mammary gland. The authors showed that expression of PIK3CA(H1047R) in lineage-committed basal Lgr5 (606667)-positive and luminal keratin-8 (KRT8; 148060)-positive cells of the adult mouse mammary gland evokes cell dedifferentiation into a multipotent stem-like state, suggesting this to be a mechanism involved in the formation of heterogeneous, multilineage mammary tumors. Moreover, Koren et al. (2015) showed that the tumor cell of origin influences the frequency of malignant mammary tumors. Koren et al. (2015) concluded that their results defined a key effect of PIK3CA(H1047R) on mammary cell fate in the preneoplastic mammary gland and showed that the cell of origin of PIK3CA(H1047R) tumors dictates their malignancy, thus revealing a mechanism underlying tumor heterogeneity and aggressiveness. Van Keymeulen et al. (2015) found that oncogenic PIK3CA(H1047R) mutant expression at physiologic levels in basal cells using keratin (K)5 (148040)-CreER(T2) mice induced the formation of luminal estrogen receptor (ER; 133430)-positive/progesterone receptor (PR; 607311)-positive tumors, while its expression in luminal cells using K8-CReER(T2) mice gave rise to luminal ER+PR+ tumors or basal-like ER-PR- tumors. Concomitant deletion of p53 (191170) and expression of Pik3ca(H1047R) accelerated tumor development and induced more aggressive mammary tumors. Interestingly, expression of Pik3ca(H1047R) in unipotent basal cells gave rise to luminal-like cells, while its expression in unipotent luminal cells gave rise to basal-like cells before progressing into invasive tumors. Transcriptional profiling of cells that underwent cell fate transition upon Pik3ca(H1047R) expression in unipotent progenitors demonstrated a profound oncogene-induced reprogramming of these newly formed cells and identified gene signatures characteristic of the different cell fate switches that occur upon Pik3ca(H1047R) expression in basal and luminal cells. Van Keymeulen et al. (2015) concluded that oncogenic Pik3ca(H1047R) activates a multipotent genetic program in normally lineage-restricted populations at the early stage of tumor initiation, setting the stage for future intratumoral heterogeneity. (less)
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Pathogenic
(Jun 24, 2012)
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no assertion criteria provided
Method: literature only
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CONGENITAL LIPOMATOUS OVERGROWTH, VASCULAR MALFORMATIONS, AND EPIDERMAL NEVI, SOMATIC
Affected status: not provided
Allele origin:
somatic
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OMIM
Accession: SCV000050487.6
First in ClinVar: Apr 04, 2013 Last updated: Oct 08, 2021 |
Comment on evidence:
Colorectal Cancer In a relatively high frequency of colorectal cancers (114500), Samuels et al. (2004) identified a his1047-to-arg (H1047R) mutation in the PIK3CA gene; in … (more)
Colorectal Cancer In a relatively high frequency of colorectal cancers (114500), Samuels et al. (2004) identified a his1047-to-arg (H1047R) mutation in the PIK3CA gene; in vitro studies showed that the H1047R mutant has increased lipid kinase activity. Breast Cancer In 5 breast tumors (114480), 7 epithelial ovarian tumors (167000), and 1 colorectal tumor from a series of 284 primary human tumors, Campbell et al. (2004) identified the H1047R mutation, which is caused by a 3140A-G transition in exon 20. Lee et al. (2005) identified a somatic H1047R mutation in 21 breast cancer tumors, 4 gastric cancer (137215) tumors, 1 hepatocellular carcinoma (114550), and 1 nonsmall cell lung cancer (211980). CLOVE Syndrome In a 2-year-old boy and an unrelated 1-year-old girl with congenital lipomatous overgrowth, vascular malformations, and epidermal nevi (CLOVE syndrome; 612918), Kurek et al. (2012) identified somatic mosaicism for the H1047R mutation in affected tissues from multiple embryonic lineages, with a mutant allele frequency ranging from 16 to 23%. Kurek et al. (2012) also stated that they had identified somatic mosaicism for H1047R in 3 patients who had been diagnosed with Klippel-Trenaunay-Weber syndrome (149000), an overgrowth syndrome with features overlapping those of CLOVE syndrome. Lindhurst et al. (2012) sequenced the PIK3CA gene in 10 individuals with an 'unclassified' syndrome of congenital progressive segmental overgrowth of fibrous and adipose tissue and bone and identified a somatic H1047R variant in 7 affected individuals, with mutation burdens ranging from less than 1% to 35% in affected tissues and fibroblast cultures. The features of the 'unclassified' syndrome were consistent with CLOVE syndrome. Seborrheic Keratosis Hafner et al. (2007) identified a heterozygous somatic H1047R mutation in a seborrheic keratosis lesion (182000). The authors emphasized that this is a benign lesion and noted that the same mutation had been observed in cancerous lesions. Macrodactyly Rios et al. (2013) identified the H1047R mutation in affected tissue from an individual (patient 6) with macrodactyly (155500). Immunochemistry showed increased staining in macrodactyly cells from patient 6 compared to control cells, indicating greater levels of ser473-phosphorylated AKT (164730) through increased activation of the PI3K-AKT cell signaling axis. Cerebral Cavernous Malformations 4 In samples of cerebral cavernous malformations-4 (CCM4; 619538) from 10 unrelated patients with sporadic occurrence of the disease, Peyre et al. (2021) identified a somatic H1047R mutation in the PIK3CA gene. The mutation was found by targeted DNA sequencing. PIK3CA-mutant CCMs showed increased phosphorylation of myosin light chain and activation of the PI3K-AKT-mTOR pathway, consistent with an activating mutation. Variant Function Using in situ genetic lineage tracing and limiting dilution transplantation, Koren et al. (2015) elucidated the potential of PIK3CA(H1047R) to induce multipotency during tumorigenesis in the mammary gland. The authors showed that expression of PIK3CA(H1047R) in lineage-committed basal Lgr5 (606667)-positive and luminal keratin-8 (KRT8; 148060)-positive cells of the adult mouse mammary gland evokes cell dedifferentiation into a multipotent stem-like state, suggesting this to be a mechanism involved in the formation of heterogeneous, multilineage mammary tumors. Moreover, Koren et al. (2015) showed that the tumor cell of origin influences the frequency of malignant mammary tumors. Koren et al. (2015) concluded that their results defined a key effect of PIK3CA(H1047R) on mammary cell fate in the preneoplastic mammary gland and showed that the cell of origin of PIK3CA(H1047R) tumors dictates their malignancy, thus revealing a mechanism underlying tumor heterogeneity and aggressiveness. Van Keymeulen et al. (2015) found that oncogenic PIK3CA(H1047R) mutant expression at physiologic levels in basal cells using keratin (K)5 (148040)-CreER(T2) mice induced the formation of luminal estrogen receptor (ER; 133430)-positive/progesterone receptor (PR; 607311)-positive tumors, while its expression in luminal cells using K8-CReER(T2) mice gave rise to luminal ER+PR+ tumors or basal-like ER-PR- tumors. Concomitant deletion of p53 (191170) and expression of Pik3ca(H1047R) accelerated tumor development and induced more aggressive mammary tumors. Interestingly, expression of Pik3ca(H1047R) in unipotent basal cells gave rise to luminal-like cells, while its expression in unipotent luminal cells gave rise to basal-like cells before progressing into invasive tumors. Transcriptional profiling of cells that underwent cell fate transition upon Pik3ca(H1047R) expression in unipotent progenitors demonstrated a profound oncogene-induced reprogramming of these newly formed cells and identified gene signatures characteristic of the different cell fate switches that occur upon Pik3ca(H1047R) expression in basal and luminal cells. Van Keymeulen et al. (2015) concluded that oncogenic Pik3ca(H1047R) activates a multipotent genetic program in normally lineage-restricted populations at the early stage of tumor initiation, setting the stage for future intratumoral heterogeneity. (less)
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Pathogenic
(Jun 24, 2012)
|
no assertion criteria provided
Method: literature only
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MACRODACTYLY, SOMATIC
Affected status: not provided
Allele origin:
somatic
|
OMIM
Accession: SCV000839591.3
First in ClinVar: Oct 14, 2018 Last updated: Oct 08, 2021 |
Comment on evidence:
Colorectal Cancer In a relatively high frequency of colorectal cancers (114500), Samuels et al. (2004) identified a his1047-to-arg (H1047R) mutation in the PIK3CA gene; in … (more)
Colorectal Cancer In a relatively high frequency of colorectal cancers (114500), Samuels et al. (2004) identified a his1047-to-arg (H1047R) mutation in the PIK3CA gene; in vitro studies showed that the H1047R mutant has increased lipid kinase activity. Breast Cancer In 5 breast tumors (114480), 7 epithelial ovarian tumors (167000), and 1 colorectal tumor from a series of 284 primary human tumors, Campbell et al. (2004) identified the H1047R mutation, which is caused by a 3140A-G transition in exon 20. Lee et al. (2005) identified a somatic H1047R mutation in 21 breast cancer tumors, 4 gastric cancer (137215) tumors, 1 hepatocellular carcinoma (114550), and 1 nonsmall cell lung cancer (211980). CLOVE Syndrome In a 2-year-old boy and an unrelated 1-year-old girl with congenital lipomatous overgrowth, vascular malformations, and epidermal nevi (CLOVE syndrome; 612918), Kurek et al. (2012) identified somatic mosaicism for the H1047R mutation in affected tissues from multiple embryonic lineages, with a mutant allele frequency ranging from 16 to 23%. Kurek et al. (2012) also stated that they had identified somatic mosaicism for H1047R in 3 patients who had been diagnosed with Klippel-Trenaunay-Weber syndrome (149000), an overgrowth syndrome with features overlapping those of CLOVE syndrome. Lindhurst et al. (2012) sequenced the PIK3CA gene in 10 individuals with an 'unclassified' syndrome of congenital progressive segmental overgrowth of fibrous and adipose tissue and bone and identified a somatic H1047R variant in 7 affected individuals, with mutation burdens ranging from less than 1% to 35% in affected tissues and fibroblast cultures. The features of the 'unclassified' syndrome were consistent with CLOVE syndrome. Seborrheic Keratosis Hafner et al. (2007) identified a heterozygous somatic H1047R mutation in a seborrheic keratosis lesion (182000). The authors emphasized that this is a benign lesion and noted that the same mutation had been observed in cancerous lesions. Macrodactyly Rios et al. (2013) identified the H1047R mutation in affected tissue from an individual (patient 6) with macrodactyly (155500). Immunochemistry showed increased staining in macrodactyly cells from patient 6 compared to control cells, indicating greater levels of ser473-phosphorylated AKT (164730) through increased activation of the PI3K-AKT cell signaling axis. Cerebral Cavernous Malformations 4 In samples of cerebral cavernous malformations-4 (CCM4; 619538) from 10 unrelated patients with sporadic occurrence of the disease, Peyre et al. (2021) identified a somatic H1047R mutation in the PIK3CA gene. The mutation was found by targeted DNA sequencing. PIK3CA-mutant CCMs showed increased phosphorylation of myosin light chain and activation of the PI3K-AKT-mTOR pathway, consistent with an activating mutation. Variant Function Using in situ genetic lineage tracing and limiting dilution transplantation, Koren et al. (2015) elucidated the potential of PIK3CA(H1047R) to induce multipotency during tumorigenesis in the mammary gland. The authors showed that expression of PIK3CA(H1047R) in lineage-committed basal Lgr5 (606667)-positive and luminal keratin-8 (KRT8; 148060)-positive cells of the adult mouse mammary gland evokes cell dedifferentiation into a multipotent stem-like state, suggesting this to be a mechanism involved in the formation of heterogeneous, multilineage mammary tumors. Moreover, Koren et al. (2015) showed that the tumor cell of origin influences the frequency of malignant mammary tumors. Koren et al. (2015) concluded that their results defined a key effect of PIK3CA(H1047R) on mammary cell fate in the preneoplastic mammary gland and showed that the cell of origin of PIK3CA(H1047R) tumors dictates their malignancy, thus revealing a mechanism underlying tumor heterogeneity and aggressiveness. Van Keymeulen et al. (2015) found that oncogenic PIK3CA(H1047R) mutant expression at physiologic levels in basal cells using keratin (K)5 (148040)-CreER(T2) mice induced the formation of luminal estrogen receptor (ER; 133430)-positive/progesterone receptor (PR; 607311)-positive tumors, while its expression in luminal cells using K8-CReER(T2) mice gave rise to luminal ER+PR+ tumors or basal-like ER-PR- tumors. Concomitant deletion of p53 (191170) and expression of Pik3ca(H1047R) accelerated tumor development and induced more aggressive mammary tumors. Interestingly, expression of Pik3ca(H1047R) in unipotent basal cells gave rise to luminal-like cells, while its expression in unipotent luminal cells gave rise to basal-like cells before progressing into invasive tumors. Transcriptional profiling of cells that underwent cell fate transition upon Pik3ca(H1047R) expression in unipotent progenitors demonstrated a profound oncogene-induced reprogramming of these newly formed cells and identified gene signatures characteristic of the different cell fate switches that occur upon Pik3ca(H1047R) expression in basal and luminal cells. Van Keymeulen et al. (2015) concluded that oncogenic Pik3ca(H1047R) activates a multipotent genetic program in normally lineage-restricted populations at the early stage of tumor initiation, setting the stage for future intratumoral heterogeneity. (less)
|
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Pathogenic
(Jun 24, 2012)
|
no assertion criteria provided
Method: literature only
|
CEREBRAL CAVERNOUS MALFORMATIONS 4, SOMATIC
Affected status: not provided
Allele origin:
somatic
|
OMIM
Accession: SCV001976535.1
First in ClinVar: Oct 08, 2021 Last updated: Oct 08, 2021 |
Comment on evidence:
Colorectal Cancer In a relatively high frequency of colorectal cancers (114500), Samuels et al. (2004) identified a his1047-to-arg (H1047R) mutation in the PIK3CA gene; in … (more)
Colorectal Cancer In a relatively high frequency of colorectal cancers (114500), Samuels et al. (2004) identified a his1047-to-arg (H1047R) mutation in the PIK3CA gene; in vitro studies showed that the H1047R mutant has increased lipid kinase activity. Breast Cancer In 5 breast tumors (114480), 7 epithelial ovarian tumors (167000), and 1 colorectal tumor from a series of 284 primary human tumors, Campbell et al. (2004) identified the H1047R mutation, which is caused by a 3140A-G transition in exon 20. Lee et al. (2005) identified a somatic H1047R mutation in 21 breast cancer tumors, 4 gastric cancer (137215) tumors, 1 hepatocellular carcinoma (114550), and 1 nonsmall cell lung cancer (211980). CLOVE Syndrome In a 2-year-old boy and an unrelated 1-year-old girl with congenital lipomatous overgrowth, vascular malformations, and epidermal nevi (CLOVE syndrome; 612918), Kurek et al. (2012) identified somatic mosaicism for the H1047R mutation in affected tissues from multiple embryonic lineages, with a mutant allele frequency ranging from 16 to 23%. Kurek et al. (2012) also stated that they had identified somatic mosaicism for H1047R in 3 patients who had been diagnosed with Klippel-Trenaunay-Weber syndrome (149000), an overgrowth syndrome with features overlapping those of CLOVE syndrome. Lindhurst et al. (2012) sequenced the PIK3CA gene in 10 individuals with an 'unclassified' syndrome of congenital progressive segmental overgrowth of fibrous and adipose tissue and bone and identified a somatic H1047R variant in 7 affected individuals, with mutation burdens ranging from less than 1% to 35% in affected tissues and fibroblast cultures. The features of the 'unclassified' syndrome were consistent with CLOVE syndrome. Seborrheic Keratosis Hafner et al. (2007) identified a heterozygous somatic H1047R mutation in a seborrheic keratosis lesion (182000). The authors emphasized that this is a benign lesion and noted that the same mutation had been observed in cancerous lesions. Macrodactyly Rios et al. (2013) identified the H1047R mutation in affected tissue from an individual (patient 6) with macrodactyly (155500). Immunochemistry showed increased staining in macrodactyly cells from patient 6 compared to control cells, indicating greater levels of ser473-phosphorylated AKT (164730) through increased activation of the PI3K-AKT cell signaling axis. Cerebral Cavernous Malformations 4 In samples of cerebral cavernous malformations-4 (CCM4; 619538) from 10 unrelated patients with sporadic occurrence of the disease, Peyre et al. (2021) identified a somatic H1047R mutation in the PIK3CA gene. The mutation was found by targeted DNA sequencing. PIK3CA-mutant CCMs showed increased phosphorylation of myosin light chain and activation of the PI3K-AKT-mTOR pathway, consistent with an activating mutation. Variant Function Using in situ genetic lineage tracing and limiting dilution transplantation, Koren et al. (2015) elucidated the potential of PIK3CA(H1047R) to induce multipotency during tumorigenesis in the mammary gland. The authors showed that expression of PIK3CA(H1047R) in lineage-committed basal Lgr5 (606667)-positive and luminal keratin-8 (KRT8; 148060)-positive cells of the adult mouse mammary gland evokes cell dedifferentiation into a multipotent stem-like state, suggesting this to be a mechanism involved in the formation of heterogeneous, multilineage mammary tumors. Moreover, Koren et al. (2015) showed that the tumor cell of origin influences the frequency of malignant mammary tumors. Koren et al. (2015) concluded that their results defined a key effect of PIK3CA(H1047R) on mammary cell fate in the preneoplastic mammary gland and showed that the cell of origin of PIK3CA(H1047R) tumors dictates their malignancy, thus revealing a mechanism underlying tumor heterogeneity and aggressiveness. Van Keymeulen et al. (2015) found that oncogenic PIK3CA(H1047R) mutant expression at physiologic levels in basal cells using keratin (K)5 (148040)-CreER(T2) mice induced the formation of luminal estrogen receptor (ER; 133430)-positive/progesterone receptor (PR; 607311)-positive tumors, while its expression in luminal cells using K8-CReER(T2) mice gave rise to luminal ER+PR+ tumors or basal-like ER-PR- tumors. Concomitant deletion of p53 (191170) and expression of Pik3ca(H1047R) accelerated tumor development and induced more aggressive mammary tumors. Interestingly, expression of Pik3ca(H1047R) in unipotent basal cells gave rise to luminal-like cells, while its expression in unipotent luminal cells gave rise to basal-like cells before progressing into invasive tumors. Transcriptional profiling of cells that underwent cell fate transition upon Pik3ca(H1047R) expression in unipotent progenitors demonstrated a profound oncogene-induced reprogramming of these newly formed cells and identified gene signatures characteristic of the different cell fate switches that occur upon Pik3ca(H1047R) expression in basal and luminal cells. Van Keymeulen et al. (2015) concluded that oncogenic Pik3ca(H1047R) activates a multipotent genetic program in normally lineage-restricted populations at the early stage of tumor initiation, setting the stage for future intratumoral heterogeneity. (less)
|
|
Pathogenic
(Jun 24, 2012)
|
no assertion criteria provided
Method: literature only
|
OVARIAN CANCER, EPITHELIAL, SOMATIC
Affected status: not provided
Allele origin:
somatic
|
OMIM
Accession: SCV000034878.6
First in ClinVar: Apr 04, 2013 Last updated: Oct 08, 2021 |
Comment on evidence:
Colorectal Cancer In a relatively high frequency of colorectal cancers (114500), Samuels et al. (2004) identified a his1047-to-arg (H1047R) mutation in the PIK3CA gene; in … (more)
Colorectal Cancer In a relatively high frequency of colorectal cancers (114500), Samuels et al. (2004) identified a his1047-to-arg (H1047R) mutation in the PIK3CA gene; in vitro studies showed that the H1047R mutant has increased lipid kinase activity. Breast Cancer In 5 breast tumors (114480), 7 epithelial ovarian tumors (167000), and 1 colorectal tumor from a series of 284 primary human tumors, Campbell et al. (2004) identified the H1047R mutation, which is caused by a 3140A-G transition in exon 20. Lee et al. (2005) identified a somatic H1047R mutation in 21 breast cancer tumors, 4 gastric cancer (137215) tumors, 1 hepatocellular carcinoma (114550), and 1 nonsmall cell lung cancer (211980). CLOVE Syndrome In a 2-year-old boy and an unrelated 1-year-old girl with congenital lipomatous overgrowth, vascular malformations, and epidermal nevi (CLOVE syndrome; 612918), Kurek et al. (2012) identified somatic mosaicism for the H1047R mutation in affected tissues from multiple embryonic lineages, with a mutant allele frequency ranging from 16 to 23%. Kurek et al. (2012) also stated that they had identified somatic mosaicism for H1047R in 3 patients who had been diagnosed with Klippel-Trenaunay-Weber syndrome (149000), an overgrowth syndrome with features overlapping those of CLOVE syndrome. Lindhurst et al. (2012) sequenced the PIK3CA gene in 10 individuals with an 'unclassified' syndrome of congenital progressive segmental overgrowth of fibrous and adipose tissue and bone and identified a somatic H1047R variant in 7 affected individuals, with mutation burdens ranging from less than 1% to 35% in affected tissues and fibroblast cultures. The features of the 'unclassified' syndrome were consistent with CLOVE syndrome. Seborrheic Keratosis Hafner et al. (2007) identified a heterozygous somatic H1047R mutation in a seborrheic keratosis lesion (182000). The authors emphasized that this is a benign lesion and noted that the same mutation had been observed in cancerous lesions. Macrodactyly Rios et al. (2013) identified the H1047R mutation in affected tissue from an individual (patient 6) with macrodactyly (155500). Immunochemistry showed increased staining in macrodactyly cells from patient 6 compared to control cells, indicating greater levels of ser473-phosphorylated AKT (164730) through increased activation of the PI3K-AKT cell signaling axis. Cerebral Cavernous Malformations 4 In samples of cerebral cavernous malformations-4 (CCM4; 619538) from 10 unrelated patients with sporadic occurrence of the disease, Peyre et al. (2021) identified a somatic H1047R mutation in the PIK3CA gene. The mutation was found by targeted DNA sequencing. PIK3CA-mutant CCMs showed increased phosphorylation of myosin light chain and activation of the PI3K-AKT-mTOR pathway, consistent with an activating mutation. Variant Function Using in situ genetic lineage tracing and limiting dilution transplantation, Koren et al. (2015) elucidated the potential of PIK3CA(H1047R) to induce multipotency during tumorigenesis in the mammary gland. The authors showed that expression of PIK3CA(H1047R) in lineage-committed basal Lgr5 (606667)-positive and luminal keratin-8 (KRT8; 148060)-positive cells of the adult mouse mammary gland evokes cell dedifferentiation into a multipotent stem-like state, suggesting this to be a mechanism involved in the formation of heterogeneous, multilineage mammary tumors. Moreover, Koren et al. (2015) showed that the tumor cell of origin influences the frequency of malignant mammary tumors. Koren et al. (2015) concluded that their results defined a key effect of PIK3CA(H1047R) on mammary cell fate in the preneoplastic mammary gland and showed that the cell of origin of PIK3CA(H1047R) tumors dictates their malignancy, thus revealing a mechanism underlying tumor heterogeneity and aggressiveness. Van Keymeulen et al. (2015) found that oncogenic PIK3CA(H1047R) mutant expression at physiologic levels in basal cells using keratin (K)5 (148040)-CreER(T2) mice induced the formation of luminal estrogen receptor (ER; 133430)-positive/progesterone receptor (PR; 607311)-positive tumors, while its expression in luminal cells using K8-CReER(T2) mice gave rise to luminal ER+PR+ tumors or basal-like ER-PR- tumors. Concomitant deletion of p53 (191170) and expression of Pik3ca(H1047R) accelerated tumor development and induced more aggressive mammary tumors. Interestingly, expression of Pik3ca(H1047R) in unipotent basal cells gave rise to luminal-like cells, while its expression in unipotent luminal cells gave rise to basal-like cells before progressing into invasive tumors. Transcriptional profiling of cells that underwent cell fate transition upon Pik3ca(H1047R) expression in unipotent progenitors demonstrated a profound oncogene-induced reprogramming of these newly formed cells and identified gene signatures characteristic of the different cell fate switches that occur upon Pik3ca(H1047R) expression in basal and luminal cells. Van Keymeulen et al. (2015) concluded that oncogenic Pik3ca(H1047R) activates a multipotent genetic program in normally lineage-restricted populations at the early stage of tumor initiation, setting the stage for future intratumoral heterogeneity. (less)
|
|
Pathogenic
(Jun 24, 2012)
|
no assertion criteria provided
Method: literature only
|
COLORECTAL CANCER, SOMATIC
Affected status: not provided
Allele origin:
somatic
|
OMIM
Accession: SCV000034879.6
First in ClinVar: Apr 04, 2013 Last updated: Oct 08, 2021 |
Comment on evidence:
Colorectal Cancer In a relatively high frequency of colorectal cancers (114500), Samuels et al. (2004) identified a his1047-to-arg (H1047R) mutation in the PIK3CA gene; in … (more)
Colorectal Cancer In a relatively high frequency of colorectal cancers (114500), Samuels et al. (2004) identified a his1047-to-arg (H1047R) mutation in the PIK3CA gene; in vitro studies showed that the H1047R mutant has increased lipid kinase activity. Breast Cancer In 5 breast tumors (114480), 7 epithelial ovarian tumors (167000), and 1 colorectal tumor from a series of 284 primary human tumors, Campbell et al. (2004) identified the H1047R mutation, which is caused by a 3140A-G transition in exon 20. Lee et al. (2005) identified a somatic H1047R mutation in 21 breast cancer tumors, 4 gastric cancer (137215) tumors, 1 hepatocellular carcinoma (114550), and 1 nonsmall cell lung cancer (211980). CLOVE Syndrome In a 2-year-old boy and an unrelated 1-year-old girl with congenital lipomatous overgrowth, vascular malformations, and epidermal nevi (CLOVE syndrome; 612918), Kurek et al. (2012) identified somatic mosaicism for the H1047R mutation in affected tissues from multiple embryonic lineages, with a mutant allele frequency ranging from 16 to 23%. Kurek et al. (2012) also stated that they had identified somatic mosaicism for H1047R in 3 patients who had been diagnosed with Klippel-Trenaunay-Weber syndrome (149000), an overgrowth syndrome with features overlapping those of CLOVE syndrome. Lindhurst et al. (2012) sequenced the PIK3CA gene in 10 individuals with an 'unclassified' syndrome of congenital progressive segmental overgrowth of fibrous and adipose tissue and bone and identified a somatic H1047R variant in 7 affected individuals, with mutation burdens ranging from less than 1% to 35% in affected tissues and fibroblast cultures. The features of the 'unclassified' syndrome were consistent with CLOVE syndrome. Seborrheic Keratosis Hafner et al. (2007) identified a heterozygous somatic H1047R mutation in a seborrheic keratosis lesion (182000). The authors emphasized that this is a benign lesion and noted that the same mutation had been observed in cancerous lesions. Macrodactyly Rios et al. (2013) identified the H1047R mutation in affected tissue from an individual (patient 6) with macrodactyly (155500). Immunochemistry showed increased staining in macrodactyly cells from patient 6 compared to control cells, indicating greater levels of ser473-phosphorylated AKT (164730) through increased activation of the PI3K-AKT cell signaling axis. Cerebral Cavernous Malformations 4 In samples of cerebral cavernous malformations-4 (CCM4; 619538) from 10 unrelated patients with sporadic occurrence of the disease, Peyre et al. (2021) identified a somatic H1047R mutation in the PIK3CA gene. The mutation was found by targeted DNA sequencing. PIK3CA-mutant CCMs showed increased phosphorylation of myosin light chain and activation of the PI3K-AKT-mTOR pathway, consistent with an activating mutation. Variant Function Using in situ genetic lineage tracing and limiting dilution transplantation, Koren et al. (2015) elucidated the potential of PIK3CA(H1047R) to induce multipotency during tumorigenesis in the mammary gland. The authors showed that expression of PIK3CA(H1047R) in lineage-committed basal Lgr5 (606667)-positive and luminal keratin-8 (KRT8; 148060)-positive cells of the adult mouse mammary gland evokes cell dedifferentiation into a multipotent stem-like state, suggesting this to be a mechanism involved in the formation of heterogeneous, multilineage mammary tumors. Moreover, Koren et al. (2015) showed that the tumor cell of origin influences the frequency of malignant mammary tumors. Koren et al. (2015) concluded that their results defined a key effect of PIK3CA(H1047R) on mammary cell fate in the preneoplastic mammary gland and showed that the cell of origin of PIK3CA(H1047R) tumors dictates their malignancy, thus revealing a mechanism underlying tumor heterogeneity and aggressiveness. Van Keymeulen et al. (2015) found that oncogenic PIK3CA(H1047R) mutant expression at physiologic levels in basal cells using keratin (K)5 (148040)-CreER(T2) mice induced the formation of luminal estrogen receptor (ER; 133430)-positive/progesterone receptor (PR; 607311)-positive tumors, while its expression in luminal cells using K8-CReER(T2) mice gave rise to luminal ER+PR+ tumors or basal-like ER-PR- tumors. Concomitant deletion of p53 (191170) and expression of Pik3ca(H1047R) accelerated tumor development and induced more aggressive mammary tumors. Interestingly, expression of Pik3ca(H1047R) in unipotent basal cells gave rise to luminal-like cells, while its expression in unipotent luminal cells gave rise to basal-like cells before progressing into invasive tumors. Transcriptional profiling of cells that underwent cell fate transition upon Pik3ca(H1047R) expression in unipotent progenitors demonstrated a profound oncogene-induced reprogramming of these newly formed cells and identified gene signatures characteristic of the different cell fate switches that occur upon Pik3ca(H1047R) expression in basal and luminal cells. Van Keymeulen et al. (2015) concluded that oncogenic Pik3ca(H1047R) activates a multipotent genetic program in normally lineage-restricted populations at the early stage of tumor initiation, setting the stage for future intratumoral heterogeneity. (less)
|
|
Pathogenic
(Jun 24, 2012)
|
no assertion criteria provided
Method: literature only
|
GASTRIC CANCER, SOMATIC
Affected status: not provided
Allele origin:
somatic
|
OMIM
Accession: SCV000034880.6
First in ClinVar: Apr 04, 2013 Last updated: Oct 08, 2021 |
Comment on evidence:
Colorectal Cancer In a relatively high frequency of colorectal cancers (114500), Samuels et al. (2004) identified a his1047-to-arg (H1047R) mutation in the PIK3CA gene; in … (more)
Colorectal Cancer In a relatively high frequency of colorectal cancers (114500), Samuels et al. (2004) identified a his1047-to-arg (H1047R) mutation in the PIK3CA gene; in vitro studies showed that the H1047R mutant has increased lipid kinase activity. Breast Cancer In 5 breast tumors (114480), 7 epithelial ovarian tumors (167000), and 1 colorectal tumor from a series of 284 primary human tumors, Campbell et al. (2004) identified the H1047R mutation, which is caused by a 3140A-G transition in exon 20. Lee et al. (2005) identified a somatic H1047R mutation in 21 breast cancer tumors, 4 gastric cancer (137215) tumors, 1 hepatocellular carcinoma (114550), and 1 nonsmall cell lung cancer (211980). CLOVE Syndrome In a 2-year-old boy and an unrelated 1-year-old girl with congenital lipomatous overgrowth, vascular malformations, and epidermal nevi (CLOVE syndrome; 612918), Kurek et al. (2012) identified somatic mosaicism for the H1047R mutation in affected tissues from multiple embryonic lineages, with a mutant allele frequency ranging from 16 to 23%. Kurek et al. (2012) also stated that they had identified somatic mosaicism for H1047R in 3 patients who had been diagnosed with Klippel-Trenaunay-Weber syndrome (149000), an overgrowth syndrome with features overlapping those of CLOVE syndrome. Lindhurst et al. (2012) sequenced the PIK3CA gene in 10 individuals with an 'unclassified' syndrome of congenital progressive segmental overgrowth of fibrous and adipose tissue and bone and identified a somatic H1047R variant in 7 affected individuals, with mutation burdens ranging from less than 1% to 35% in affected tissues and fibroblast cultures. The features of the 'unclassified' syndrome were consistent with CLOVE syndrome. Seborrheic Keratosis Hafner et al. (2007) identified a heterozygous somatic H1047R mutation in a seborrheic keratosis lesion (182000). The authors emphasized that this is a benign lesion and noted that the same mutation had been observed in cancerous lesions. Macrodactyly Rios et al. (2013) identified the H1047R mutation in affected tissue from an individual (patient 6) with macrodactyly (155500). Immunochemistry showed increased staining in macrodactyly cells from patient 6 compared to control cells, indicating greater levels of ser473-phosphorylated AKT (164730) through increased activation of the PI3K-AKT cell signaling axis. Cerebral Cavernous Malformations 4 In samples of cerebral cavernous malformations-4 (CCM4; 619538) from 10 unrelated patients with sporadic occurrence of the disease, Peyre et al. (2021) identified a somatic H1047R mutation in the PIK3CA gene. The mutation was found by targeted DNA sequencing. PIK3CA-mutant CCMs showed increased phosphorylation of myosin light chain and activation of the PI3K-AKT-mTOR pathway, consistent with an activating mutation. Variant Function Using in situ genetic lineage tracing and limiting dilution transplantation, Koren et al. (2015) elucidated the potential of PIK3CA(H1047R) to induce multipotency during tumorigenesis in the mammary gland. The authors showed that expression of PIK3CA(H1047R) in lineage-committed basal Lgr5 (606667)-positive and luminal keratin-8 (KRT8; 148060)-positive cells of the adult mouse mammary gland evokes cell dedifferentiation into a multipotent stem-like state, suggesting this to be a mechanism involved in the formation of heterogeneous, multilineage mammary tumors. Moreover, Koren et al. (2015) showed that the tumor cell of origin influences the frequency of malignant mammary tumors. Koren et al. (2015) concluded that their results defined a key effect of PIK3CA(H1047R) on mammary cell fate in the preneoplastic mammary gland and showed that the cell of origin of PIK3CA(H1047R) tumors dictates their malignancy, thus revealing a mechanism underlying tumor heterogeneity and aggressiveness. Van Keymeulen et al. (2015) found that oncogenic PIK3CA(H1047R) mutant expression at physiologic levels in basal cells using keratin (K)5 (148040)-CreER(T2) mice induced the formation of luminal estrogen receptor (ER; 133430)-positive/progesterone receptor (PR; 607311)-positive tumors, while its expression in luminal cells using K8-CReER(T2) mice gave rise to luminal ER+PR+ tumors or basal-like ER-PR- tumors. Concomitant deletion of p53 (191170) and expression of Pik3ca(H1047R) accelerated tumor development and induced more aggressive mammary tumors. Interestingly, expression of Pik3ca(H1047R) in unipotent basal cells gave rise to luminal-like cells, while its expression in unipotent luminal cells gave rise to basal-like cells before progressing into invasive tumors. Transcriptional profiling of cells that underwent cell fate transition upon Pik3ca(H1047R) expression in unipotent progenitors demonstrated a profound oncogene-induced reprogramming of these newly formed cells and identified gene signatures characteristic of the different cell fate switches that occur upon Pik3ca(H1047R) expression in basal and luminal cells. Van Keymeulen et al. (2015) concluded that oncogenic Pik3ca(H1047R) activates a multipotent genetic program in normally lineage-restricted populations at the early stage of tumor initiation, setting the stage for future intratumoral heterogeneity. (less)
|
|
Pathogenic
(Jun 24, 2012)
|
no assertion criteria provided
Method: literature only
|
KERATOSIS, SEBORRHEIC, SOMATIC
Affected status: not provided
Allele origin:
somatic
|
OMIM
Accession: SCV000034883.6
First in ClinVar: Apr 04, 2013 Last updated: Oct 08, 2021 |
Comment on evidence:
Colorectal Cancer In a relatively high frequency of colorectal cancers (114500), Samuels et al. (2004) identified a his1047-to-arg (H1047R) mutation in the PIK3CA gene; in … (more)
Colorectal Cancer In a relatively high frequency of colorectal cancers (114500), Samuels et al. (2004) identified a his1047-to-arg (H1047R) mutation in the PIK3CA gene; in vitro studies showed that the H1047R mutant has increased lipid kinase activity. Breast Cancer In 5 breast tumors (114480), 7 epithelial ovarian tumors (167000), and 1 colorectal tumor from a series of 284 primary human tumors, Campbell et al. (2004) identified the H1047R mutation, which is caused by a 3140A-G transition in exon 20. Lee et al. (2005) identified a somatic H1047R mutation in 21 breast cancer tumors, 4 gastric cancer (137215) tumors, 1 hepatocellular carcinoma (114550), and 1 nonsmall cell lung cancer (211980). CLOVE Syndrome In a 2-year-old boy and an unrelated 1-year-old girl with congenital lipomatous overgrowth, vascular malformations, and epidermal nevi (CLOVE syndrome; 612918), Kurek et al. (2012) identified somatic mosaicism for the H1047R mutation in affected tissues from multiple embryonic lineages, with a mutant allele frequency ranging from 16 to 23%. Kurek et al. (2012) also stated that they had identified somatic mosaicism for H1047R in 3 patients who had been diagnosed with Klippel-Trenaunay-Weber syndrome (149000), an overgrowth syndrome with features overlapping those of CLOVE syndrome. Lindhurst et al. (2012) sequenced the PIK3CA gene in 10 individuals with an 'unclassified' syndrome of congenital progressive segmental overgrowth of fibrous and adipose tissue and bone and identified a somatic H1047R variant in 7 affected individuals, with mutation burdens ranging from less than 1% to 35% in affected tissues and fibroblast cultures. The features of the 'unclassified' syndrome were consistent with CLOVE syndrome. Seborrheic Keratosis Hafner et al. (2007) identified a heterozygous somatic H1047R mutation in a seborrheic keratosis lesion (182000). The authors emphasized that this is a benign lesion and noted that the same mutation had been observed in cancerous lesions. Macrodactyly Rios et al. (2013) identified the H1047R mutation in affected tissue from an individual (patient 6) with macrodactyly (155500). Immunochemistry showed increased staining in macrodactyly cells from patient 6 compared to control cells, indicating greater levels of ser473-phosphorylated AKT (164730) through increased activation of the PI3K-AKT cell signaling axis. Cerebral Cavernous Malformations 4 In samples of cerebral cavernous malformations-4 (CCM4; 619538) from 10 unrelated patients with sporadic occurrence of the disease, Peyre et al. (2021) identified a somatic H1047R mutation in the PIK3CA gene. The mutation was found by targeted DNA sequencing. PIK3CA-mutant CCMs showed increased phosphorylation of myosin light chain and activation of the PI3K-AKT-mTOR pathway, consistent with an activating mutation. Variant Function Using in situ genetic lineage tracing and limiting dilution transplantation, Koren et al. (2015) elucidated the potential of PIK3CA(H1047R) to induce multipotency during tumorigenesis in the mammary gland. The authors showed that expression of PIK3CA(H1047R) in lineage-committed basal Lgr5 (606667)-positive and luminal keratin-8 (KRT8; 148060)-positive cells of the adult mouse mammary gland evokes cell dedifferentiation into a multipotent stem-like state, suggesting this to be a mechanism involved in the formation of heterogeneous, multilineage mammary tumors. Moreover, Koren et al. (2015) showed that the tumor cell of origin influences the frequency of malignant mammary tumors. Koren et al. (2015) concluded that their results defined a key effect of PIK3CA(H1047R) on mammary cell fate in the preneoplastic mammary gland and showed that the cell of origin of PIK3CA(H1047R) tumors dictates their malignancy, thus revealing a mechanism underlying tumor heterogeneity and aggressiveness. Van Keymeulen et al. (2015) found that oncogenic PIK3CA(H1047R) mutant expression at physiologic levels in basal cells using keratin (K)5 (148040)-CreER(T2) mice induced the formation of luminal estrogen receptor (ER; 133430)-positive/progesterone receptor (PR; 607311)-positive tumors, while its expression in luminal cells using K8-CReER(T2) mice gave rise to luminal ER+PR+ tumors or basal-like ER-PR- tumors. Concomitant deletion of p53 (191170) and expression of Pik3ca(H1047R) accelerated tumor development and induced more aggressive mammary tumors. Interestingly, expression of Pik3ca(H1047R) in unipotent basal cells gave rise to luminal-like cells, while its expression in unipotent luminal cells gave rise to basal-like cells before progressing into invasive tumors. Transcriptional profiling of cells that underwent cell fate transition upon Pik3ca(H1047R) expression in unipotent progenitors demonstrated a profound oncogene-induced reprogramming of these newly formed cells and identified gene signatures characteristic of the different cell fate switches that occur upon Pik3ca(H1047R) expression in basal and luminal cells. Van Keymeulen et al. (2015) concluded that oncogenic Pik3ca(H1047R) activates a multipotent genetic program in normally lineage-restricted populations at the early stage of tumor initiation, setting the stage for future intratumoral heterogeneity. (less)
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
Breast carcinoma
Affected status: yes
Allele origin:
somatic
|
Medical Oncology, Institut Jules Bordet
Accession: SCV003803732.1
First in ClinVar: Feb 25, 2023 Last updated: Feb 25, 2023 |
Sex: female
|
|
Likely pathogenic
(Mar 19, 2024)
|
no assertion criteria provided
Method: clinical testing
|
Rare venous malformation
Affected status: yes
Allele origin:
somatic
|
Institute of Tissue Medicine and Pathology, University of Bern
Accession: SCV005038944.1
First in ClinVar: May 07, 2024 Last updated: May 07, 2024 |
Number of individuals with the variant: 3
|
|
Likely pathogenic
(Mar 19, 2024)
|
no assertion criteria provided
Method: clinical testing
|
Rare combined vascular malformation
Affected status: yes
Allele origin:
somatic
|
Institute of Tissue Medicine and Pathology, University of Bern
Accession: SCV005038945.1
First in ClinVar: May 07, 2024 Last updated: May 07, 2024 |
Number of individuals with the variant: 1
|
|
Pathogenic
(Aug 05, 2010)
|
no assertion criteria provided
Method: clinical testing
|
Non-Small Cell Lung Cancer
Affected status: not provided
Allele origin:
somatic
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000199905.1
First in ClinVar: Jan 31, 2015 Last updated: Jan 31, 2015 |
Number of individuals with the variant: 12
|
|
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: SCV000504110.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Pancreatic adenocarcinoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000504117.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely pathogenic
(Jul 14, 2015)
|
no assertion criteria provided
Method: literature only
|
Neoplasm
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000504119.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Adrenal cortex carcinoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000504118.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Carcinoma of esophagus
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000504116.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Pathogenic
(Oct 02, 2014)
|
no assertion criteria provided
Method: literature only
|
Neoplasm of ovary
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000504120.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
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: SCV000504121.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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Likely pathogenic
(May 31, 2016)
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no assertion criteria provided
Method: literature only
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Prostate adenocarcinoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
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Database of Curated Mutations (DoCM)
Accession: SCV000504125.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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Likely pathogenic
(May 31, 2016)
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no assertion criteria provided
Method: literature only
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Hepatocellular carcinoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
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Database of Curated Mutations (DoCM)
Accession: SCV000504122.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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Likely pathogenic
(May 31, 2016)
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no assertion criteria provided
Method: literature only
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Medulloblastoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
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Database of Curated Mutations (DoCM)
Accession: SCV000504123.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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Likely pathogenic
(May 31, 2016)
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no assertion criteria provided
Method: literature only
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Neoplasm of brain
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
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Database of Curated Mutations (DoCM)
Accession: SCV000504124.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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Likely pathogenic
(May 31, 2016)
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no assertion criteria provided
Method: literature only
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Renal cell carcinoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
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Database of Curated Mutations (DoCM)
Accession: SCV000504127.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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Likely pathogenic
(May 31, 2016)
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no assertion criteria provided
Method: literature only
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None
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000504126.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
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Glioblastoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000504131.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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Likely pathogenic
(May 31, 2016)
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no assertion criteria provided
Method: literature only
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Gastric adenocarcinoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
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Database of Curated Mutations (DoCM)
Accession: SCV000504128.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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Likely pathogenic
(May 31, 2016)
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no assertion criteria provided
Method: literature only
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Squamous cell lung carcinoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
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Database of Curated Mutations (DoCM)
Accession: SCV000504129.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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Likely pathogenic
(May 31, 2016)
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no assertion criteria provided
Method: literature only
|
None
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000504130.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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Pathogenic
(Apr 30, 2019)
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no assertion criteria provided
Method: research
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Lip and oral cavity carcinoma
Affected status: yes
Allele origin:
somatic
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Institute of Medical Sciences, Banaras Hindu University
Accession: SCV001432251.1
First in ClinVar: Sep 18, 2020 Last updated: Sep 18, 2020 |
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Pathogenic
(-)
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no assertion criteria provided
Method: provider interpretation
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Abnormal cardiovascular system morphology
Affected status: yes
Allele origin:
somatic
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MAGI's Lab - Research, MAGI Group
Accession: SCV001437644.1
First in ClinVar: Mar 18, 2021 Last updated: Mar 18, 2021 |
Observation 1: Observation 2: Observation 3: Observation 4: Observation 5: |
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Pathogenic
(Sep 30, 2021)
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no assertion criteria provided
Method: clinical testing
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Cerebrofacial Vascular Metameric Syndrome (CVMS)
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
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James Bennett Lab, Seattle Childrens Research Institute
Accession: SCV001960168.1
First in ClinVar: Oct 21, 2021 Last updated: Oct 21, 2021 |
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Pathogenic
(Jun 02, 2022)
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no assertion criteria provided
Method: clinical testing
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CLOVES syndrome
Affected status: yes
Allele origin:
germline
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Clinical Genetics Laboratory, University Hospital Schleswig-Holstein
Accession: SCV002583480.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022 |
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not provided
(-)
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no classification provided
Method: literature only
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CLOVES syndrome
Affected status: not provided
Allele origin:
unknown
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GeneReviews
Accession: SCV000086944.2
First in ClinVar: Oct 01, 2013 Last updated: Oct 01, 2022 |
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Germline Functional Evidence
Functional
Help
The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
Help
A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
Help
A brief description of the result of this method for 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 functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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effect on protein activity
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Biesecker Lab Rare Disease, National Institutes of Health
Accession: SCV000898478.1
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gain_of_function_variant
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James Bennett Lab, Seattle Childrens Research Institute
Accession: SCV001960168.1
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Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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PIK3CA-Related Overgrowth Spectrum. | Adam MP | - | 2023 | PMID: 23946963 |
Somatic PIK3CA Mutations in Sporadic Cerebral Cavernous Malformations. | Peyre M | The New England journal of medicine | 2021 | PMID: 34496175 |
Phenotype-driven variant filtration strategy in exome sequencing toward a high diagnostic yield and identification of 85 novel variants in 400 patients with rare Mendelian disorders. | Marinakis NM | American journal of medical genetics. Part A | 2021 | PMID: 34008892 |
Genotype correlates with clinical severity in PIK3CA-associated lymphatic malformations. | Zenner K | JCI insight | 2019 | PMID: 31536475 |
Molecular heterogeneity of the cerebriform connective tissue nevus in mosaic overgrowth syndromes. | Keppler-Noreuil KM | Cold Spring Harbor molecular case studies | 2019 | PMID: 31371346 |
PIK3CA c.3140A>G mutation in a patient with suspected Proteus Syndrome: a case report. | Valentini V | Clinical case reports | 2018 | PMID: 29988677 |
A Phase Ib Study of Alpelisib (BYL719), a PI3Kα-Specific Inhibitor, with Letrozole in ER+/HER2- Metastatic Breast Cancer. | Mayer IA | Clinical cancer research : an official journal of the American Association for Cancer Research | 2017 | PMID: 27126994 |
Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity. | Chang MT | Nature biotechnology | 2016 | PMID: 26619011 |
Identification of Variant-Specific Functions of PIK3CA by Rapid Phenotyping of Rare Mutations. | Dogruluk T | Cancer research | 2015 | PMID: 26627007 |
Reactivation of multipotency by oncogenic PIK3CA induces breast tumour heterogeneity. | Van Keymeulen A | Nature | 2015 | PMID: 26266985 |
PIK3CA(H1047R) induces multipotency and multi-lineage mammary tumours. | Koren S | Nature | 2015 | PMID: 26266975 |
Prospective enterprise-level molecular genotyping of a cohort of cancer patients. | MacConaill LE | The Journal of molecular diagnostics : JMD | 2014 | PMID: 25157968 |
Somatic gain-of-function mutations in PIK3CA in patients with macrodactyly. | Rios JJ | Human molecular genetics | 2013 | PMID: 23100325 |
Conditional activation of Pik3ca(H1047R) in a knock-in mouse model promotes mammary tumorigenesis and emergence of mutations. | Yuan W | Oncogene | 2013 | PMID: 22370636 |
Mosaic overgrowth with fibroadipose hyperplasia is caused by somatic activating mutations in PIK3CA. | Lindhurst MJ | Nature genetics | 2012 | PMID: 22729222 |
Somatic mosaic activating mutations in PIK3CA cause CLOVES syndrome. | Kurek KC | American journal of human genetics | 2012 | PMID: 22658544 |
PI3K/AKT/mTOR inhibitors in patients with breast and gynecologic malignancies harboring PIK3CA mutations. | Janku F | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2012 | PMID: 22271473 |
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 |
The selective class I PI3K inhibitor CH5132799 targets human cancers harboring oncogenic PIK3CA mutations. | Tanaka H | Clinical cancer research : an official journal of the American Association for Cancer Research | 2011 | PMID: 21558396 |
Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. | Sequist LV | Science translational medicine | 2011 | PMID: 21430269 |
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 |
Structural effects of oncogenic PI3Kα mutations. | Gabelli SB | Current topics in microbiology and immunology | 2010 | PMID: 20593314 |
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 |
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 |
A novel dual PI3Kalpha/mTOR inhibitor PI-103 with high antitumor activity in non-small cell lung cancer cells. | Zou ZQ | International journal of molecular medicine | 2009 | PMID: 19513541 |
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 |
PIK3CA mutations in colorectal cancer are associated with clinical resistance to EGFR-targeted monoclonal antibodies. | Sartore-Bianchi A | Cancer research | 2009 | PMID: 19223544 |
Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers. | Engelman JA | Nature medicine | 2008 | PMID: 19029981 |
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 |
Oncogenic PIK3CA mutations occur in epidermal nevi and seborrheic keratoses with a characteristic mutation pattern. | Hafner C | Proceedings of the National Academy of Sciences of the United States of America | 2007 | PMID: 17673550 |
Allelic dilution obscures detection of a biologically significant resistance mutation in EGFR-amplified lung cancer. | Engelman JA | The Journal of clinical investigation | 2006 | PMID: 16906227 |
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 |
PIK3CA gene is frequently mutated in breast carcinomas and hepatocellular carcinomas. | Lee JW | Oncogene | 2005 | PMID: 15608678 |
Mutation of the PIK3CA gene in ovarian and breast cancer. | Campbell IG | Cancer research | 2004 | PMID: 15520168 |
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.3140A>G | - | - | - | - |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/f4d8f50e-a120-47e5-8b69-0a8921149fde | - | - | - | - |
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Text-mined citations for rs121913279 ...
HelpRecord last updated May 12, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.