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NM_006218.4(PIK3CA):c.1357G>A (p.Glu453Lys) AND Cowden syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 14, 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:
RCV001861479.13

Allele description [Variation Report for NM_006218.4(PIK3CA):c.1357G>A (p.Glu453Lys)]

NM_006218.4(PIK3CA):c.1357G>A (p.Glu453Lys)

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.1357G>A (p.Glu453Lys)
HGVS:
  • NC_000003.12:g.179210291G>A
  • NG_012113.2:g.66769G>A
  • NM_006218.4:c.1357G>AMANE SELECT
  • NP_006209.2:p.Glu453Lys
  • LRG_310t1:c.1357G>A
  • LRG_310:g.66769G>A
  • NC_000003.11:g.178928079G>A
  • NM_006218.2:c.1357G>A
  • NM_006218.3:c.1357G>A
  • p.E453K
Protein change:
E453K
Links:
dbSNP: rs1057519925
NCBI 1000 Genomes Browser:
rs1057519925
Molecular consequence:
  • NM_006218.4:c.1357G>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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002247469Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jun 14, 2021) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

PIK3CA-associated developmental disorders exhibit distinct classes of mutations with variable expression and tissue distribution.

Mirzaa G, Timms AE, Conti V, Boyle EA, Girisha KM, Martin B, Kircher M, Olds C, Juusola J, Collins S, Park K, Carter M, Glass I, Krägeloh-Mann I, Chitayat D, Parikh AS, Bradshaw R, Torti E, Braddock S, Burke L, Ghedia S, Stephan M, et al.

JCI Insight. 2016 Jun 16;1(9). doi:pii: 87623. 10.1172/jci.insight.87623.

PubMed [citation]
PMID:
27631024
PMCID:
PMC5019182

Molecular diagnosis of PIK3CA-related overgrowth spectrum (PROS) in 162 patients and recommendations for genetic testing.

Kuentz P, St-Onge J, Duffourd Y, Courcet JB, Carmignac V, Jouan T, Sorlin A, Abasq-Thomas C, Albuisson J, Amiel J, Amram D, Arpin S, Attie-Bitach T, Bahi-Buisson N, Barbarot S, Baujat G, Bessis D, Boccara O, Bonnière M, Boute O, Bursztejn AC, Chiaverini C, et al.

Genet Med. 2017 Sep;19(9):989-997. doi: 10.1038/gim.2016.220. Epub 2017 Feb 2.

PubMed [citation]
PMID:
28151489
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV002247469.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces glutamic acid with lysine at codon 453 of the PIK3CA protein (p.Glu453Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with PIK3CA-associated overgrowth conditions (PMID: 27631024, 27631024, 28151489, ClinVar). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 376470). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 19, 2024