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NM_001382430.1(AKT1):c.49G>A (p.Glu17Lys) AND Breast adenocarcinoma

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 18, 2011
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV000015017.4

Allele description [Variation Report for NM_001382430.1(AKT1):c.49G>A (p.Glu17Lys)]

NM_001382430.1(AKT1):c.49G>A (p.Glu17Lys)

Gene:
AKT1:AKT serine/threonine kinase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
14q32.33
Genomic location:
Preferred name:
NM_001382430.1(AKT1):c.49G>A (p.Glu17Lys)
HGVS:
  • NC_000014.9:g.104780214C>T
  • NG_012188.1:g.20531G>A
  • NM_001014431.2:c.49G>A
  • NM_001014432.2:c.49G>A
  • NM_001382430.1:c.49G>AMANE SELECT
  • NM_001382431.1:c.49G>A
  • NM_001382432.1:c.49G>A
  • NM_001382433.1:c.49G>A
  • NM_005163.2:c.49G>A
  • NP_001014431.1:p.Glu17Lys
  • NP_001014432.1:p.Glu17Lys
  • NP_001369359.1:p.Glu17Lys
  • NP_001369360.1:p.Glu17Lys
  • NP_001369361.1:p.Glu17Lys
  • NP_001369362.1:p.Glu17Lys
  • NP_005154.2:p.Glu17Lys
  • LRG_721t2:c.49G>A
  • LRG_721:g.20531G>A
  • LRG_721p2:p.Glu17Lys
  • NC_000014.8:g.105246551C>T
  • NM_001382430.1:c.49G>A
  • P31749:p.Glu17Lys
Protein change:
E17K; GLU17LYS
Links:
UniProtKB: P31749#VAR_055422; OMIM: 164730.0001; dbSNP: rs121434592
NCBI 1000 Genomes Browser:
rs121434592
Molecular consequence:
  • NM_001014431.2:c.49G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001014432.2:c.49G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001382430.1:c.49G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001382431.1:c.49G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001382432.1:c.49G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001382433.1:c.49G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_005163.2:c.49G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Breast adenocarcinoma
Synonyms:
Breast cancer, somatic; Breast adenocarcinoma, somatic
Identifiers:
MONDO: MONDO:0004988; MedGen: C0858252

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000035273OMIM
no assertion criteria provided
Pathogenic
(Aug 18, 2011) 		somaticliterature only

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedsomaticnot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

A transforming mutation in the pleckstrin homology domain of AKT1 in cancer.

Carpten JD, Faber AL, Horn C, Donoho GP, Briggs SL, Robbins CM, Hostetter G, Boguslawski S, Moses TY, Savage S, Uhlik M, Lin A, Du J, Qian YW, Zeckner DJ, Tucker-Kellogg G, Touchman J, Patel K, Mousses S, Bittner M, Schevitz R, Lai MH, et al.

Nature. 2007 Jul 26;448(7152):439-44. Epub 2007 Jul 4.

PubMed [citation]
PMID:
17611497

A mosaic activating mutation in AKT1 associated with the Proteus syndrome.

Lindhurst MJ, Sapp JC, Teer JK, Johnston JJ, Finn EM, Peters K, Turner J, Cannons JL, Bick D, Blakemore L, Blumhorst C, Brockmann K, Calder P, Cherman N, Deardorff MA, Everman DB, Golas G, Greenstein RM, Kato BM, Keppler-Noreuil KM, Kuznetsov SA, Miyamoto RT, et al.

N Engl J Med. 2011 Aug 18;365(7):611-9. doi: 10.1056/NEJMoa1104017. Epub 2011 Jul 27.

PubMed [citation]
PMID:
21793738
PMCID:
PMC3170413

Details of each submission

From OMIM, SCV000035273.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

Carpten et al. (2007) identified a 49G-A transition in the AKT1 gene, resulting in a glu17-to-lys (E17K) substitution, in tumor specimens from 5 of 61 (8%) breast cancer (114480) samples, 3 of 51 (6%) colorectal cancers (114500), and 1 of 50 (2%) ovarian cancers (167000). DNA from normal adjacent tissue or white blood cells showed no evidence of this mutation, which occurs in the PHD domain of AKT1. The AKT1 mutation was mutually exclusive with respect to mutations in PIK3CA (171834) and complete loss of PTEN (601728) protein expression. Carpten et al. (2007) showed that this mutation alters the AKT1-PHD conformation, results in activation of AKT1, and alters the subcellular location of AKT1 to the plasma membrane. Furthermore, Carpten et al. (2007) found that the AKT1 containing the E17K mutation was able to transform cells in culture and induce leukemia in mice.

Lindhurst et al. (2011) performed exome sequencing of 11 DNA samples from 6 patients with Proteus syndrome (176920), as well as 1 sample each from 5 unaffected parents and from 1 patient's unaffected identical twin sib, and identified an activating E17K mutation in the AKT1 gene in 7 samples from 3 patients. The association was confirmed using a custom restriction-enzyme assay: overall, 26 (90%) of 29 patients with Proteus syndrome who were tested carried the E17K mutation in one or more samples, with the fraction of mutant DNA in the positive specimens ranging from 1% to approximately 50%. Mutant cell lines demonstrated greater AKT phosphorylation than control cell lines, and single-cell clones established from the same starting culture but differing in mutation status had different levels of AKT phosphorylation.

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

Last Updated: Sep 29, 2024