NM_006218.4(PIK3CA):c.3139_3140delinsAT (p.His1047Ile) AND Cowden syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 16, 2020
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:: RCV001352011.6

Allele description [Variation Report for NM_006218.4(PIK3CA):c.3139_3140delinsAT (p.His1047Ile)]

NM_006218.4(PIK3CA):c.3139_3140delinsAT (p.His1047Ile)

Gene:

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

Variant type:

Indel

Cytogenetic location:

3q26.32

Genomic location:

Preferred name:

NM_006218.4(PIK3CA):c.3139_3140delinsAT (p.His1047Ile)

HGVS:

NC_000003.12:g.179234296_179234297delinsAT
NG_012113.2:g.90774_90775delinsAT
NM_006218.4:c.3139_3140delinsATMANE SELECT
NP_006209.2:p.His1047Ile
LRG_310:g.90774_90775delinsAT
NC_000003.11:g.178952084_178952085delinsAT

Protein change:

H1047I

Links:

dbSNP: rs1725283257

NCBI 1000 Genomes Browser:

rs1725283257

Molecular consequence:

NM_006218.4:c.3139_3140delinsAT - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001546528	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 16, 2020)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 25599672, 27631024, 28502725, 22658544, 23100325, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001546528

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 16, 2020)

germline

clinical testing

PubMed (6)
[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

Mammalian target of rapamycin pathway mutations cause hemimegalencephaly and focal cortical dysplasia.

D'Gama AM, Geng Y, Couto JA, Martin B, Boyle EA, LaCoursiere CM, Hossain A, Hatem NE, Barry BJ, Kwiatkowski DJ, Vinters HV, Barkovich AJ, Shendure J, Mathern GW, Walsh CA, Poduri A.

Ann Neurol. 2015 Apr;77(4):720-5. doi: 10.1002/ana.24357. Epub 2015 Feb 26.

PubMed [citation]

PMID:: 25599672
PMCID:: PMC4471336

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

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001546528.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PIK3CA-related conditions. 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: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available"). This variant disrupts the p.His1047 amino acid residue in PIK3CA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 25599672, 27631024, 28502725, 22658544, 23100325). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This sequence change replaces histidine with isoleucine at codon 1047 of the PIK3CA protein (p.His1047Ile). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and isoleucine.

#	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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