NM_006218.4(PIK3CA):c.3140A>T (p.His1047Leu) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 27, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002254265.4

Allele description [Variation Report for NM_006218.4(PIK3CA):c.3140A>T (p.His1047Leu)]

NM_006218.4(PIK3CA):c.3140A>T (p.His1047Leu)

Gene:

PIK3CA:phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3q26.32

Genomic location:

Preferred name:

NM_006218.4(PIK3CA):c.3140A>T (p.His1047Leu)

HGVS:

NC_000003.12:g.179234297A>T
NG_012113.2:g.90775A>T
NM_006218.4:c.3140A>TMANE SELECT
NP_006209.2:p.His1047Leu
LRG_310t1:c.3140A>T
LRG_310:g.90775A>T
NC_000003.11:g.178952085A>T
NM_006218.2:c.3140A>T
NM_006218.3:c.3140A>T
P42336:p.His1047Leu

Protein change:

H1047L; HIS1047LEU

Links:

UniProtKB: P42336#VAR_026191; OMIM: 171834.0002; dbSNP: rs121913279

NCBI 1000 Genomes Browser:

rs121913279

Molecular consequence:

NM_006218.4:c.3140A>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002525712	Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 27, 2021)	somatic	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002525712

Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 27, 2021)

somatic

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	somatic	yes	4	not provided	not provided	4	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital, SCV002525712.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (1)
2	not provided	1	not provided	not provided	clinical testing	PubMed (1)
3	not provided	1	not provided	not provided	clinical testing	PubMed (1)
4	not provided	1	not provided	not provided	clinical testing	PubMed (1)

Description

This variant has previously been reported in numerous unrelated individuals with PIK3CA-related segmental overgrowth syndrome, including individuals with venous malformations (PMID: 25681199, PMID: 27631024, PMID: 28151489, NBK153722). The p.H1047L variant substitutes the histidine with leucine at position 1047 within the PIK3CA kinase domain. This is an activating mutation that results in ligand-independent activation of the PI3K-AKT-mTOR pathway and increased proliferation in vitro (PMID: 26627007).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	somatic	yes	1	not provided	not provided		1	not provided	not provided	not provided
2	somatic	yes	1	not provided	not provided		1	not provided	not provided	not provided
3	somatic	yes	1	not provided	not provided		1	not provided	not provided	not provided
4	somatic	yes	1	not provided	not provided		1	not provided	not provided	not provided

Last Updated: May 12, 2024

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