NM_006218.4(PIK3CA):c.3131A>G (p.Asn1044Ser) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jul 20, 2015
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000479562.3

Allele description [Variation Report for NM_006218.4(PIK3CA):c.3131A>G (p.Asn1044Ser)]

NM_006218.4(PIK3CA):c.3131A>G (p.Asn1044Ser)

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.3131A>G (p.Asn1044Ser)

HGVS:

NC_000003.12:g.179234288A>G
NG_012113.2:g.90766A>G
NM_006218.4:c.3131A>GMANE SELECT
NP_006209.2:p.Asn1044Ser
LRG_310t1:c.3131A>G
LRG_310:g.90766A>G
NC_000003.11:g.178952076A>G
NM_006218.2:c.3131A>G

Protein change:

N1044S

Links:

dbSNP: rs1064793838

NCBI 1000 Genomes Browser:

rs1064793838

Molecular consequence:

NM_006218.4:c.3131A>G - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000567156	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Jul 20, 2015)	germline	clinical testing	Citation Link,
SCV002568843	Laboratoire de Génétique Moléculaire, CHU Bordeaux	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	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

SCV000567156

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Jul 20, 2015)

germline

clinical testing

Citation Link,

SCV002568843

Laboratoire de Génétique Moléculaire, CHU Bordeaux

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

germline

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	germline	yes	not provided	not provided	not provided	not provided	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 GeneDx, SCV000567156.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The N1044S substitution in the PIK3CA gene has not been reported previously as a pathogenic variantnor as a benign polymorphism, to our knowledge. The N1044S variant was not observed in approximately6000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project,indicating it is not a common benign variant in these populations. The N1044S variant is a conservativeamino acid substitution and occurs at a position that is conserved across species. In silico analysis isinconsistent in its predictions as to whether or not the variant is damaging to the proteinstructure/function. Missense variants in nearby residues (A1035V, M1043I, H1047Y, G1049S) havebeen reported in the Human Gene Mutation Database in association with megalencephaly-capillarymalformation (Stenson et al., 2014), supporting the functional importance of this region of the protein. Weinterpret N1044S as a pathogenic variant.

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

From Laboratoire de Génétique Moléculaire, CHU Bordeaux, SCV002568843.1

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

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

Last Updated: Oct 12, 2025

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