NM_006218.4(PIK3CA):c.3129G>A (p.Met1043Ile) AND Cowden syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 5, 2022
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:: RCV000699681.8

Allele description [Variation Report for NM_006218.4(PIK3CA):c.3129G>A (p.Met1043Ile)]

NM_006218.4(PIK3CA):c.3129G>A (p.Met1043Ile)

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.3129G>A (p.Met1043Ile)

HGVS:

NC_000003.12:g.179234286G>A
NG_012113.2:g.90764G>A
NM_006218.4:c.3129G>AMANE SELECT
NP_006209.2:p.Met1043Ile
LRG_310t1:c.3129G>A
LRG_310:g.90764G>A
NC_000003.11:g.178952074G>A
NM_006218.2:c.3129G>A
P42336:p.Met1043Ile

Protein change:

M1043I

Links:

UniProtKB: P42336#VAR_026190; dbSNP: rs121913283

NCBI 1000 Genomes Browser:

rs121913283

Molecular consequence:

NM_006218.4:c.3129G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cowden syndrome (CS)
Synonyms:: Cowden's disease; Cowden's syndrome; Cowden disease; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0016063; MedGen: C0018553; Orphanet: 201; OMIM: PS158350

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Coelops frithii recombination activator protein 2 (RAG2) gene, partial cds
Coelops frithii recombination activator protein 2 (RAG2) gene, partial cds
gi|763551867|gb|KP176027.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000828404	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 5, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 15930273, 17376864, 22120714, 28151489, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000828404

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 5, 2022)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Functional analysis of PIK3CA gene mutations in human colorectal cancer.

Ikenoue T, Kanai F, Hikiba Y, Obata T, Tanaka Y, Imamura J, Ohta M, Jazag A, Guleng B, Tateishi K, Asaoka Y, Matsumura M, Kawabe T, Omata M.

Cancer Res. 2005 Jun 1;65(11):4562-7.

PubMed [citation]

PMID:: 15930273

Rare cancer-specific mutations in PIK3CA show gain of function.

Gymnopoulos M, Elsliger MA, Vogt PK.

Proc Natl Acad Sci U S A. 2007 Mar 27;104(13):5569-74. Epub 2007 Mar 21.

PubMed [citation]

PMID:: 17376864
PMCID:: PMC1838453

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000828404.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects PIK3CA function (PMID: 15930273, 17376864, 22120714). 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) performed at Invitae indicates that this missense variant is expected to disrupt PIK3CA protein function. ClinVar contains an entry for this variant (Variation ID: 179173). This missense change has been observed in individual(s) with hemimegalencephaly (PMID: 28151489). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1043 of the PIK3CA protein (p.Met1043Ile).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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