ClinVar Genomic variation as it relates to human health
NM_006218.4(PIK3CA):c.1624G>A (p.Glu542Lys)
No data submitted for somatic clinical impact
The aggregate oncogenicity classification for this variant for one or more tumor types, using the ClinGen/CGC/VICC terminology. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate oncogenicity classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Variant Details
- Identifiers
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NM_006218.4(PIK3CA):c.1624G>A (p.Glu542Lys)
Variation ID: 31944 Accession: VCV000031944.34
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 3q26.32 3: 179218294 (GRCh38) [ NCBI UCSC ] 3: 178936082 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Oct 8, 2024 Feb 12, 2022 Somatic - Oncogenicity Aug 11, 2024 Aug 11, 2024 Jul 31, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_006218.4:c.1624G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_006209.2:p.Glu542Lys missense NC_000003.12:g.179218294G>A NC_000003.11:g.178936082G>A NG_012113.2:g.74772G>A LRG_310:g.74772G>A LRG_310t1:c.1624G>A P42336:p.Glu542Lys - Protein change
- E542K
- Other names
- NM_006218.3(PIK3CA):c.1624G>A
- NM_006218.4(PIK3CA):c.1624G>A
- Canonical SPDI
- NC_000003.12:179218293:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- gain_of_function_variant Sequence Ontology [SO:0002053]
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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
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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 |
1292 | 1326 |
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/Likely pathogenic (3) |
no assertion criteria provided
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Mar 19, 2024 | RCV000024622.22 | |
Pathogenic (3) |
no assertion criteria provided
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Dec 1, 2018 | RCV000151649.15 | |
Pathogenic (2) |
no assertion criteria provided
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Oct 2, 2014 | RCV000154513.14 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Feb 27, 2023 | RCV000416776.15 | |
Likely pathogenic (1) |
no assertion criteria provided
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May 31, 2016 | RCV000431000.9 | |
Pathogenic (1) |
no assertion criteria provided
|
May 31, 2016 | RCV000431872.9 | |
Likely pathogenic (1) |
no assertion criteria provided
|
May 31, 2016 | RCV000436932.9 | |
Likely pathogenic (1) |
no assertion criteria provided
|
May 31, 2016 | RCV000438815.9 | |
Likely pathogenic (1) |
no assertion criteria provided
|
May 31, 2016 | RCV000441707.9 | |
Pathogenic (1) |
no assertion criteria provided
|
May 31, 2016 | RCV000442348.10 | |
Likely pathogenic (1) |
no assertion criteria provided
|
May 31, 2016 | RCV000419905.9 | |
Likely pathogenic (1) |
no assertion criteria provided
|
May 31, 2016 | RCV000420078.9 | |
Likely pathogenic (1) |
no assertion criteria provided
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May 31, 2016 | RCV000426691.9 | |
Likely pathogenic (1) |
no assertion criteria provided
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May 31, 2016 | RCV000433007.9 | |
Likely pathogenic (1) |
no assertion criteria provided
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May 31, 2016 | RCV000419440.9 | |
Likely pathogenic (1) |
no assertion criteria provided
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May 31, 2016 | RCV000421639.9 | |
Likely pathogenic (1) |
no assertion criteria provided
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May 31, 2016 | RCV000425548.9 | |
Likely pathogenic (1) |
no assertion criteria provided
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May 31, 2016 | RCV000430763.9 | |
Likely pathogenic (1) |
no assertion criteria provided
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May 31, 2016 | RCV000435811.9 | |
Likely pathogenic (1) |
no assertion criteria provided
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May 31, 2016 | RCV000445059.9 | |
Pathogenic (1) |
no assertion criteria provided
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Jun 8, 2012 | RCV000709693.14 | |
Pathogenic (1) |
no assertion criteria provided
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Apr 30, 2019 | RCV001255687.9 | |
CEREBRAL CAVERNOUS MALFORMATIONS 4, SOMATIC
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Pathogenic (1) |
no assertion criteria provided
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Jun 8, 2012 | RCV001728093.12 |
Pathogenic (1) |
no assertion criteria provided
|
- | RCV001327962.9 | |
Cerebrofacial Vascular Metameric Syndrome (CVMS)
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Pathogenic (1) |
no assertion criteria provided
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Sep 30, 2021 | RCV001730477.9 |
Pathogenic (1) |
reviewed by expert panel
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Feb 12, 2022 | RCV001836714.10 | |
PIK3CA-related overgrowth
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not provided (1) |
no classification provided
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- | RCV003987334.2 |
Pathogenic (1) |
criteria provided, single submitter
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Nov 3, 2023 | RCV003458190.2 | |
Pathogenic (1) |
criteria provided, single submitter
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Oct 27, 2022 | RCV002513230.10 | |
PIK3CA-related disorder
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Pathogenic (1) |
no assertion criteria provided
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Jul 24, 2024 | RCV004532404.3 |
Pathogenic (1) |
criteria provided, single submitter
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- | RCV004698785.1 | |
Likely pathogenic (1) |
no assertion criteria provided
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Mar 19, 2024 | RCV004527296.1 | |
HEMIFACIAL MYOHYPERPLASIA, SOMATIC
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Pathogenic (1) |
no assertion criteria provided
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Jun 8, 2012 | RCV003764635.2 |
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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 12, 2022)
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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
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ClinGen Brain Malformations Variant Curation Expert Panel
FDA Recognized Database
Accession: SCV001949964.2 First in ClinVar: Oct 02, 2021 Last updated: Feb 20, 2022 |
Comment:
The c.1624G>A (NM_006218.4) variant in PIK3CA is a missense variant predicted to cause substitution of (p.Glu542Lys). Testing of unaffected and affected tissue show variable allelic … (more)
The c.1624G>A (NM_006218.4) variant in PIK3CA is a missense variant predicted to cause substitution of (p.Glu542Lys). Testing of unaffected and affected tissue show variable allelic fractions consistent with a post-zygotic event (PS2_Moderate; PMID: 22658544). The prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls (PS4_VS; PMIDs: 25722288, 25681199, 22658544, 29446767, 26851524, 25292196, 23100325; identified in 1 individual with neuroimaging demonstrating at least one large cerebral hemisphere with cortical malformation, at least 6 individuals with a clinical diagnosis of megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome; (MPPH) or megalencephaly-capillary malformation-polymicrogyria syndrome; (MCAP), at least 9 individuals with segmental overgrowth or vascular malformation of a limb or region of the body, and at least 9 tumor samples in the literature and COSMIC). This variant is absent from gnomAD v2.1.1 (PM2_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). 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: PS2_M, PS4_VS, PM2_P, PP2; 12 points (VCEP specifications version 1; Approved: 1/31/2021) (less)
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Megalencephaly-capillary malformation-polymicrogyria syndrome
Affected status: yes
Allele origin:
germline
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Genetics and Personalized Medicine Clinic, Tartu University Hospital
Accession: SCV005199861.1
First in ClinVar: Sep 08, 2024 Last updated: Sep 08, 2024 |
Clinical Features:
Lymphangioma (present) , 3-4 toe syndactyly (present) , Macrodactyly of toe (present)
Age: 0-9 years
Sex: female
Ethnicity/Population group: Estonian
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Pathogenic
(Oct 01, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
somatic,
germline
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Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital
Accession: SCV002525701.1
First in ClinVar: Jun 11, 2022 Last updated: Jun 11, 2022 |
Comment:
This variant has previously been reported in several unrelated individuals with PIK3CA-related segmental overgrowth syndrome (PMID: 31536475, PMID: 25681199, PMID: 29985963 and others). The p.E542K … (more)
This variant has previously been reported in several unrelated individuals with PIK3CA-related segmental overgrowth syndrome (PMID: 31536475, PMID: 25681199, PMID: 29985963 and others). The p.E542K variant substitutes the glutamic acid at position 542 with lysine within the PIK helical domain of the PIK3CA protein (UniProt P42336). This is an activating mutation that results in ligand-independent activation of the PI3K-AKT-mTOR pathway and increased proliferation in vitro (PMID: 26627007). (less)
Observation 1:
Number of individuals with the variant: 1
Clinical Features:
Venous malformation (present)
Observation 2:
Number of individuals with the variant: 1
Clinical Features:
Abnormality of the vasculature (present) , Facial asymmetry (present) , Multiple lipomas (present)
Observation 3:
Number of individuals with the variant: 1
Clinical Features:
Abnormal lymphatic vessel morphology (present) , Eczematoid dermatitis (present) , Dental malocclusion (present) , Facial asymmetry (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) , Cerebral venous angioma (present) , Abnormal vascular morphology (present) , Headache (present)
Observation 6:
Number of individuals with the variant: 1
Clinical Features:
Abnormal lymphatic vessel morphology (present) , Venous malformation (present) , Overgrowth (present)
Observation 7:
Number of individuals with the variant: 1
Clinical Features:
Abnormal lymphatic vessel morphology (present)
Observation 8:
Number of individuals with the variant: 1
Clinical Features:
Abnormal lymphatic vessel morphology (present) , Capillary malformation (present) , Congenital macrodactylia (present) , Nevus (present) , Abnormality of the upper limb (present) , Abnormality … (more)
Abnormal lymphatic vessel morphology (present) , Capillary malformation (present) , Congenital macrodactylia (present) , Nevus (present) , Abnormality of the upper limb (present) , Abnormality of the shoulder girdle musculature (present) (less)
Observation 9:
Number of individuals with the variant: 1
Observation 10:
Number of individuals with the variant: 1
Observation 11:
Number of individuals with the variant: 1
Observation 12:
Number of individuals with the variant: 1
Observation 13:
Number of individuals with the variant: 1
Clinical Features:
Abnormal lymphatic vessel morphology (present)
Observation 14:
Number of individuals with the variant: 1
Clinical Features:
Abnormal lymphatic vessel morphology (present)
Observation 15:
Number of individuals with the variant: 1
Clinical Features:
Abnormal lymphatic vessel morphology (present)
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
Observation 19:
Number of individuals with the variant: 1
Observation 20:
Number of individuals with the variant: 1
Clinical Features:
Abnormal lymphatic vessel morphology (present)
Observation 21:
Number of individuals with the variant: 1
Clinical Features:
Lymphangioma (present)
Observation 22:
Number of individuals with the variant: 1
Clinical Features:
Overgrowth (present) , Capillary malformation (present)
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Pathogenic
(Feb 27, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001830827.4
First in ClinVar: Sep 08, 2021 Last updated: Mar 11, 2023 |
Comment:
Not observed at significant frequency in large population cohorts (gnomAD); Classified as pathogenic by the ClinGen Brain Malformations Variant Curation Expert Panel (SCV001949964.2); In silico … (more)
Not observed at significant frequency in large population cohorts (gnomAD); Classified as pathogenic by the ClinGen Brain Malformations Variant Curation Expert Panel (SCV001949964.2); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 25599672, 25044986, 29446767, 27631024, 26851524, 23100325, 23066039, 22658544, 22357840, 24374682, 33502802, 34606700) (less)
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Pathogenic
(Nov 03, 2023)
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criteria provided, single submitter
Method: clinical testing
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PIK3CA-related overgrowth syndrome
Affected status: yes
Allele origin:
somatic
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Clinical Genomics Laboratory, Washington University in St. Louis
Accession: SCV004176951.1
First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023 |
Comment:
A PIK3CA c.1624G>A (p.Glu542Lys) variant was identified at an allelic fraction consistent with somatic origin. This variant has been reported in numerous individuals with PIK3CA-Related … (more)
A PIK3CA c.1624G>A (p.Glu542Lys) variant was identified at an allelic fraction consistent with somatic origin. This variant has been reported in numerous individuals with PIK3CA-Related Overgrowth Spectrum (PROS) disorders (Yeung KS et al., PMID: 28328134; Rodriguez-Laguna L et al., PMID: 29446767; Mirzaa G et al., PMID: 27631024; Osborn AJ et al., PMID: 25292196; Kurek KC et al., PMID: 22658544; McNulty SN et al., PMID: 31585106; Luks VL et al., PMID: 25681199). The PIK3CA c.1624G>A (p.Glu542Lys) variant has been classified as a pathogenic variant both in a germline and a somatic state by numerous laboratories as well as by an expert panel as a germline pathogenic variant (ClinVar Variation ID: 31944). This variant resides within the helical domain of the p110⍺ catalytic subunit, amino acids 517-694, of PIK3CA that is defined as a critical functional domain and constitutes a mutational hotspot (Madsen R et al., PMID: 30197175; Gymnopoulos M et al., PMID: 17376864). The PIK3CA c.1624G>A (p.Glu542Lys) variant is absent from the general population (gnomAD v.3.1.2), indicating it is not a common variant. Functional studies show that this lysine substitution at codon 542 leads to increased lipid kinase activity of p110a, autonomous phosphorylation of AKT, and oncogenic cellular transformation, indicating that this variant impacts protein function (Gymnopoulos M et al., PMID: 17376864; Ikenoue T et al., PMID: 15930273; Kang S et al., PMID: 15647370). The PIK3CA gene is defined by the ClinGen Brain Malformations Variant Curation 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 (Lai A et al., PMID: 35997716). A large number of PI3K/AKT pathway inhibitors are currently under clinical study, in both PROS disorders and cancer (Jin N et al., PMID: 34779417; Venot Q et al., PMID: 29899452; Parker VER et al., PMID: 30270358). Based on an internally-developed protocol informed by the ACMG/AMP guidelines (Richards S et al., PMID: 25741868) and gene-specific practices from the ClinGen Criteria Specification Registry, the PIK3CA c.1624G>A (p.Glu542Lys) variant is classified as pathogenic. (less)
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Pathogenic
(Oct 27, 2022)
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criteria provided, single submitter
Method: clinical testing
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Cowden syndrome
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV003525379.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 542 of the PIK3CA protein … (more)
This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 542 of the PIK3CA protein (p.Glu542Lys). This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PIK3CA protein function. ClinVar contains an entry for this variant (Variation ID: 31944). This missense change has been observed in individual(s) with PIK3CA-related disorders (PMID: 25599672, 26851524, 27631024). In at least one individual the variant was observed to be de novo. (less)
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Pathogenic
(Sep 01, 2015)
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no assertion criteria provided
Method: case-control
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not provided
Affected status: yes
Allele origin:
somatic
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Department of Medical Genetics, University of Szeged
Accession: SCV000258982.1
First in ClinVar: Feb 10, 2017 Last updated: Feb 10, 2017 |
Clinical Features:
Macrodactyly of fingers (present)
Indication for testing: Macrodactyly of fingers
Family history: no
Age: 0-9 years
Sex: female
Ethnicity/Population group: Caucasian
Geographic origin: Hungary
Tissue: soft tissue
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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: SCV001432252.1
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: SCV001437638.1
First in ClinVar: Mar 18, 2021 Last updated: Mar 18, 2021 |
Observation 1: Observation 2: |
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Pathogenic
(Jun 08, 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
|
OMIM
Accession: SCV000050488.5
First in ClinVar: Apr 04, 2013 Last updated: Mar 10, 2024 |
Comment on evidence:
CLOVE Syndrome In a 14-year-old girl and an unrelated 1-year-old boy with CLOVE syndrome (612918), Kurek et al. (2012) identified somatic mosaicism for a 1624G-A … (more)
CLOVE Syndrome In a 14-year-old girl and an unrelated 1-year-old boy with CLOVE syndrome (612918), Kurek et al. (2012) identified somatic mosaicism for a 1624G-A transition in the PIK3CA gene, resulting in a glu542-to-lys (E542K) substitution that was present in affected tissues from multiple embryonic lineages with a mutant allele frequency ranging from 6 to 13%. CLAPO Syndrome In tissue from a lower lip capillary malformation (CM) from a 2-year-old female patient (P10) with CLAPO syndrome (613089), Rodriguez-Laguna et al. (2018) identified a c.1624G-A transition (c.1624G-A, NM_006218.2) in the PIK3CA gene that resulted in a glu542-to-lys (E542K) mutation in the helical domain. The mutation was present at an allele frequency of 10% by deep sequencing, was present in 999 samples from the Catalogue of Somatic Mutations in Cancer (COSMIC) database, and had been previously reported in 44 patients with vascular overgrowth disorders. Functional studies were not performed. Cerebral Cavernous Malformations 4 In samples of cerebral cavernous malformations-4 (CCM4; 619538) from 16 unrelated patients with sporadic occurrence of the disease, Peyre et al. (2021) identified a somatic E542K 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. Hemifacial Myohyperplasia In 2 patients (patients 3 and 4) with hemifacial myohyperplasia (HFMH; 606773), Bayard et al. (2023) identified mosaicism for the E542K mutation in the PIK3CA gene. Bayard et al. (2023) performed genotyping on muscle biopsies from affected regions and found a mutation burden of 12% in patient 3 and 21% in patient 4. (less)
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Pathogenic
(Jun 08, 2012)
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no assertion criteria provided
Method: literature only
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CAPILLARY MALFORMATION OF THE LOWER LIP, LYMPHATIC MALFORMATION OF FACE AND NECK, ASYMMETRY OF FACE AND LIMBS, AND PARTIAL/GENERALIZED OVERGROWTH, SOMATIC
Affected status: not provided
Allele origin:
somatic
|
OMIM
Accession: SCV000839593.4
First in ClinVar: Oct 14, 2018 Last updated: Mar 10, 2024 |
Comment on evidence:
CLOVE Syndrome In a 14-year-old girl and an unrelated 1-year-old boy with CLOVE syndrome (612918), Kurek et al. (2012) identified somatic mosaicism for a 1624G-A … (more)
CLOVE Syndrome In a 14-year-old girl and an unrelated 1-year-old boy with CLOVE syndrome (612918), Kurek et al. (2012) identified somatic mosaicism for a 1624G-A transition in the PIK3CA gene, resulting in a glu542-to-lys (E542K) substitution that was present in affected tissues from multiple embryonic lineages with a mutant allele frequency ranging from 6 to 13%. CLAPO Syndrome In tissue from a lower lip capillary malformation (CM) from a 2-year-old female patient (P10) with CLAPO syndrome (613089), Rodriguez-Laguna et al. (2018) identified a c.1624G-A transition (c.1624G-A, NM_006218.2) in the PIK3CA gene that resulted in a glu542-to-lys (E542K) mutation in the helical domain. The mutation was present at an allele frequency of 10% by deep sequencing, was present in 999 samples from the Catalogue of Somatic Mutations in Cancer (COSMIC) database, and had been previously reported in 44 patients with vascular overgrowth disorders. Functional studies were not performed. Cerebral Cavernous Malformations 4 In samples of cerebral cavernous malformations-4 (CCM4; 619538) from 16 unrelated patients with sporadic occurrence of the disease, Peyre et al. (2021) identified a somatic E542K 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. Hemifacial Myohyperplasia In 2 patients (patients 3 and 4) with hemifacial myohyperplasia (HFMH; 606773), Bayard et al. (2023) identified mosaicism for the E542K mutation in the PIK3CA gene. Bayard et al. (2023) performed genotyping on muscle biopsies from affected regions and found a mutation burden of 12% in patient 3 and 21% in patient 4. (less)
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Pathogenic
(Jun 08, 2012)
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no assertion criteria provided
Method: literature only
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CEREBRAL CAVERNOUS MALFORMATIONS 4, SOMATIC
Affected status: not provided
Allele origin:
somatic
|
OMIM
Accession: SCV001976537.2
First in ClinVar: Oct 08, 2021 Last updated: Mar 10, 2024 |
Comment on evidence:
CLOVE Syndrome In a 14-year-old girl and an unrelated 1-year-old boy with CLOVE syndrome (612918), Kurek et al. (2012) identified somatic mosaicism for a 1624G-A … (more)
CLOVE Syndrome In a 14-year-old girl and an unrelated 1-year-old boy with CLOVE syndrome (612918), Kurek et al. (2012) identified somatic mosaicism for a 1624G-A transition in the PIK3CA gene, resulting in a glu542-to-lys (E542K) substitution that was present in affected tissues from multiple embryonic lineages with a mutant allele frequency ranging from 6 to 13%. CLAPO Syndrome In tissue from a lower lip capillary malformation (CM) from a 2-year-old female patient (P10) with CLAPO syndrome (613089), Rodriguez-Laguna et al. (2018) identified a c.1624G-A transition (c.1624G-A, NM_006218.2) in the PIK3CA gene that resulted in a glu542-to-lys (E542K) mutation in the helical domain. The mutation was present at an allele frequency of 10% by deep sequencing, was present in 999 samples from the Catalogue of Somatic Mutations in Cancer (COSMIC) database, and had been previously reported in 44 patients with vascular overgrowth disorders. Functional studies were not performed. Cerebral Cavernous Malformations 4 In samples of cerebral cavernous malformations-4 (CCM4; 619538) from 16 unrelated patients with sporadic occurrence of the disease, Peyre et al. (2021) identified a somatic E542K 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. Hemifacial Myohyperplasia In 2 patients (patients 3 and 4) with hemifacial myohyperplasia (HFMH; 606773), Bayard et al. (2023) identified mosaicism for the E542K mutation in the PIK3CA gene. Bayard et al. (2023) performed genotyping on muscle biopsies from affected regions and found a mutation burden of 12% in patient 3 and 21% in patient 4. (less)
|
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Pathogenic
(Jun 08, 2012)
|
no assertion criteria provided
Method: literature only
|
HEMIFACIAL MYOHYPERPLASIA, SOMATIC
Affected status: not provided
Allele origin:
somatic
|
OMIM
Accession: SCV004697482.2
First in ClinVar: Mar 05, 2024 Last updated: Mar 10, 2024 |
Comment on evidence:
CLOVE Syndrome In a 14-year-old girl and an unrelated 1-year-old boy with CLOVE syndrome (612918), Kurek et al. (2012) identified somatic mosaicism for a 1624G-A … (more)
CLOVE Syndrome In a 14-year-old girl and an unrelated 1-year-old boy with CLOVE syndrome (612918), Kurek et al. (2012) identified somatic mosaicism for a 1624G-A transition in the PIK3CA gene, resulting in a glu542-to-lys (E542K) substitution that was present in affected tissues from multiple embryonic lineages with a mutant allele frequency ranging from 6 to 13%. CLAPO Syndrome In tissue from a lower lip capillary malformation (CM) from a 2-year-old female patient (P10) with CLAPO syndrome (613089), Rodriguez-Laguna et al. (2018) identified a c.1624G-A transition (c.1624G-A, NM_006218.2) in the PIK3CA gene that resulted in a glu542-to-lys (E542K) mutation in the helical domain. The mutation was present at an allele frequency of 10% by deep sequencing, was present in 999 samples from the Catalogue of Somatic Mutations in Cancer (COSMIC) database, and had been previously reported in 44 patients with vascular overgrowth disorders. Functional studies were not performed. Cerebral Cavernous Malformations 4 In samples of cerebral cavernous malformations-4 (CCM4; 619538) from 16 unrelated patients with sporadic occurrence of the disease, Peyre et al. (2021) identified a somatic E542K 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. Hemifacial Myohyperplasia In 2 patients (patients 3 and 4) with hemifacial myohyperplasia (HFMH; 606773), Bayard et al. (2023) identified mosaicism for the E542K mutation in the PIK3CA gene. Bayard et al. (2023) performed genotyping on muscle biopsies from affected regions and found a mutation burden of 12% in patient 3 and 21% in patient 4. (less)
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pathologic
(Aug 15, 2013)
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no assertion criteria provided
Method: curation
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PIK3CA-Related Segmental Overgrowth
Affected status: not provided
Allele origin:
not provided
|
GeneReviews
Accession: SCV000086942.1
First in ClinVar: Oct 01, 2013 Last updated: Oct 01, 2013 |
Comment:
Converted during submission to Pathogenic.
|
|
Pathogenic
(Oct 12, 2011)
|
no assertion criteria provided
Method: clinical testing
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Ovarian Cancer
Affected status: not provided
Allele origin:
somatic
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000199901.1
First in ClinVar: Jan 31, 2015 Last updated: Jan 31, 2015 |
Number of individuals with the variant: 2
|
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Pathogenic
(Oct 12, 2011)
|
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: SCV000204184.1
First in ClinVar: Jan 31, 2015 Last updated: Jan 31, 2015 |
Number of individuals with the variant: 7
|
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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: SCV000503916.1
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 brain
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000503917.1
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: SCV000503918.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
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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: SCV000503919.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Pathogenic
(Oct 02, 2014)
|
no assertion criteria provided
Method: literature only
|
Ovarian neoplasm
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000503920.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Glioblastoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000503921.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Hepatocellular carcinoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000503922.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
None
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000503923.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Papillary renal cell carcinoma, sporadic
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000503924.1
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: SCV000503925.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Prostate adenocarcinoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000503926.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Squamous cell lung carcinoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000503927.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Gastric adenocarcinoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000503928.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Small cell lung carcinoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000503929.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
None
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000503930.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Malignant neoplasm of body of uterus
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000503931.1
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: SCV000503932.1
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: SCV000503933.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Pathogenic
(Sep 30, 2021)
|
no assertion criteria provided
Method: clinical testing
|
Cerebrofacial Vascular Metameric Syndrome (CVMS)
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
James Bennett Lab, Seattle Childrens Research Institute
Accession: SCV001960169.1
First in ClinVar: Oct 21, 2021 Last updated: Oct 21, 2021 |
|
|
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: SCV005038938.1
First in ClinVar: May 07, 2024 Last updated: May 07, 2024 |
Number of individuals with the variant: 5
|
|
Likely pathogenic
(Mar 19, 2024)
|
no assertion criteria provided
Method: clinical testing
|
CLOVES syndrome
Affected status: yes
Allele origin:
somatic
|
Institute of Tissue Medicine and Pathology, University of Bern
Accession: SCV005038939.1
First in ClinVar: May 07, 2024 Last updated: May 07, 2024 |
Number of individuals with the variant: 1
|
|
Pathogenic
(Jul 24, 2024)
|
no assertion criteria provided
Method: clinical testing
|
PIK3CA-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV004717831.2
First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024 |
Comment:
The PIK3CA c.1624G>A variant is predicted to result in the amino acid substitution p.Glu542Lys. This is a recurrent somatic variant reported in individuals with dysplastic … (more)
The PIK3CA c.1624G>A variant is predicted to result in the amino acid substitution p.Glu542Lys. This is a recurrent somatic variant reported in individuals with dysplastic megalencephaly, hemimegalencephaly, or CLOVES syndrome (Kurek et al. 2012. PubMed ID: 22658544; Mirzaa et al. 2013. PubMed ID: 23946963; D’Gama et al. 2015. PubMed ID: 25599672; Mirzaa et al. 2016. PubMed ID: 27631024). This variant has not been reported in a large population database, indicating this variant is rare. This variant is interpreted as pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/31944/). This variant is interpreted as pathogenic. (less)
|
|
Pathogenic
(Dec 01, 2018)
|
no assertion criteria provided
Method: research
|
Ovarian neoplasm
Affected status: yes
Allele origin:
somatic
|
German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne
Accession: SCV000923935.1
First in ClinVar: Jun 17, 2019 Last updated: Jun 17, 2019 |
|
|
not provided
(-)
|
no classification provided
Method: phenotyping only
|
PIK3CA-related overgrowth
Affected status: unknown
Allele origin:
unknown
|
GenomeConnect - Brain Gene Registry
Accession: SCV004804559.1
First in ClinVar: Mar 30, 2024 Last updated: Mar 30, 2024 |
Comment:
Variant classified as Pathogenic and reported on 06-14-2017 by Clinical Genomics Lab at Washington University in St. Louis. Assertions are reported exactly as they appear … (more)
Variant classified as Pathogenic and reported on 06-14-2017 by Clinical Genomics Lab at Washington University in St. Louis. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator Dr. Philip Payne from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/. (less)
Clinical Features:
Cystic hygroma (present) , Abnormality of the lymphatic system (present) , Developmental dysplasia of the hip (present)
Age: 0-9 years
Sex: female
Method: Single Gene Sequencing
Testing laboratory: Clinical Genomics Laboratory, Washington University in St. Louis
Date variant was reported to submitter: 2017-06-14
Testing laboratory interpretation: Pathogenic
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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. |
---|---|---|---|---|
gain_of_function_variant
|
James Bennett Lab, Seattle Childrens Research Institute
Accession: SCV001960169.1
|
|
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Hemifacial myohyperplasia is due to somatic muscular PIK3CA gain-of-function mutations and responds to pharmacological inhibition. | Bayard C | The Journal of experimental medicine | 2023 | PMID: 37712948 |
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 |
Genotype correlates with clinical severity in PIK3CA-associated lymphatic malformations. | Zenner K | JCI insight | 2019 | PMID: 31536475 |
CLAPO syndrome: identification of somatic activating PIK3CA mutations and delineation of the natural history and phenotype. | Rodriguez-Laguna L | Genetics in medicine : official journal of the American College of Medical Genetics | 2018 | PMID: 29446767 |
PIK3CA-associated developmental disorders exhibit distinct classes of mutations with variable expression and tissue distribution. | Mirzaa G | JCI insight | 2016 | PMID: 27631024 |
Somatic mosaicism of the PIK3CA gene identified in a Hungarian girl with macrodactyly and syndactyly. | Tripolszki K | European journal of medical genetics | 2016 | PMID: 26851524 |
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 |
Mammalian target of rapamycin pathway mutations cause hemimegalencephaly and focal cortical dysplasia. | D'Gama AM | Annals of neurology | 2015 | PMID: 25599672 |
Prospective enterprise-level molecular genotyping of a cohort of cancer patients. | MacConaill LE | The Journal of molecular diagnostics : JMD | 2014 | PMID: 25157968 |
Regorafenib in metastatic colorectal cancer. | Sartore-Bianchi A | Expert review of anticancer therapy | 2014 | PMID: 24559322 |
PIK3CA mutation H1047R is associated with response to PI3K/AKT/mTOR signaling pathway inhibitors in early-phase clinical trials. | Janku F | Cancer research | 2013 | PMID: 23066039 |
Somatic mosaic activating mutations in PIK3CA cause CLOVES syndrome. | Kurek KC | American journal of human genetics | 2012 | PMID: 22658544 |
Prognostic role of PIK3CA mutation in colorectal cancer: cohort study and literature review. | Liao X | Clinical cancer research : an official journal of the American Association for Cancer Research | 2012 | PMID: 22357840 |
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 |
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 |
PIK3CA mutation status in Japanese lung cancer patients. | Kawano O | Lung cancer (Amsterdam, Netherlands) | 2006 | PMID: 16930767 |
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 |
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.1624G>A | - | - | - | - |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/7ffcf400-d46a-4637-be35-8721447aa249 | - | - | - | - |
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Conditions - Somatic
Tumor type
Help
The tumor type for this variant-condition (RCV) record in ClinVar. |
Clinical impact (# of submissions)
Help
The aggregate somatic clinical impact for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to the aggregate somatic clinical impact is shown in parentheses. The corresponding review status for the RCV record is indicated by stars. Read our rules for calculating the review status. |
Oncogenicity
Help
The aggregate oncogenicity classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to the aggregate oncogenicity classification is shown in parentheses. The corresponding review status for the RCV record is indicated by stars. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the tumor type. |
Variation/condition record
Help
The most recent date that a submitter evaluated this variant for the tumor type. |
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Oncogenic
criteria provided, single submitter
|
Jul 31, 2024 | RCV004668742.1 |
Submissions - Somatic
Oncogenicity
Help
The submitted oncogenicity classification for each SCV record. (Last evaluated) |
Review Status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. |
Tumor type
Help
The tumor type for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the somatic clinical impact, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Oncogenic
(Jul 31, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Neoplasm
Affected status: unknown
Allele origin:
somatic
|
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV005094532.1
First In ClinVar: Aug 11, 2024 Last updated: Aug 11, 2024 |
|
Citations for somatic classification of this variant
HelpThere are no citations for somatic classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs121913273 ...
HelpRecord last updated Oct 08, 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.