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Genetic epilepsy syndromes

Gene: AKT1

Red List (low evidence)

AKT1 (AKT serine/threonine kinase 1)
EnsemblGeneIds (GRCh38): ENSG00000142208
EnsemblGeneIds (GRCh37): ENSG00000142208
OMIM: 164730, Gene2Phenotype
AKT1 is in 11 panels

5 reviews

Rebecca Foulger (Genomics England curator)

I don't know

As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed to demote AKT1 from Green to Red. This panel is not the appropriate test for somatic variant detection due to the coverage. R110 Segmental overgrowth disorders (panel #98) should be used where megalencephaly is present to allow detection of somatic mosaic mutations.
Created: 15 Aug 2019, 10:23 a.m. | Last Modified: 15 Aug 2019, 10:23 a.m.
Panel Version: 1.233
Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Red. Technical notes: PI3K/AKT pathway mutations can cause a spectrum of brain malformations that lead to seizures; however, these are likely to be somatic mutations. Would WGS be appropriate for this pathway for peripheral blood?.
Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189

Tracy Lester (Genetics laboratory, Oxford UK)

Red List (low evidence)

PI3K/AKT pathway mutations can cause a spectrum of brain malformations that lead to seizures. however, these are likely to be somatic mutations. Would WGS be appropriate for this pathway for peripheral blood? Somatic Proteus syndrome. In addition somatic variants have been linked to Breast, colorectal, ovarian cancer and Cowden syndrome 6). Proteus syndrome - highly variable, severe disorder of asymmetric and disprop overgrowth of body parts. References used on panel app: Cohen, 2014 - review of molecular, clinical and pathological features - caused by an activating AKT1 mutation - Glu17Lys - seizures have been reported as a feature. If this is a somatic variant - surely we would have to test the affected tissue to detect the variant -? Include as may not be detectable in blood - Lindhurst et al, 2011 paper - only 2/38 peripheral blood samples collected from Proteus syndrome patients were positive for the mutation and that a molecualr diagnosis with the use of peripheral blood DNA may be challenging.
Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188

Phenotypes
Breast cancer, somatic, 114480; Colorectal cancer, somatic, 114500; Cowden syndrome, 615109; Ovarian cancer, somatic, 167000; Proteus syndrome, somatic 176920; {Schizophrenia, susceptibility to} 181500

Publications

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Somatic mutations, multiple patients reported, seizures part of the phenotype. Recurrent mutation is activating.
Created: 7 Aug 2018, 9:10 a.m.

Mode of inheritance
Other

Publications

Mode of pathogenicity
Other

Variants in this GENE are reported as part of current diagnostic practice

Sarah Leigh (Genomics England Curator)

Comment on mode of inheritance: Somatic mosaicism
Created: 27 Sep 2018, 9:04 a.m.
Comment on mode of pathogenicity: somatic mosaic activating variants
Created: 26 Sep 2018, 2:58 p.m.
Comment on mode of inheritance: Somatic variants
Created: 16 Jul 2018, 3:53 p.m.

Arianna Tucci (Genomics England Curator)

Green List (high evidence)

Proteus syndrome is associated with mosaicism for a somatic activating mutation in the AKT1 gene. Epilepsy can be part of phenotype
Created: 4 Jul 2018, 9:46 p.m.

Mode of inheritance
Other

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Red
  • Wessex and West Midlands GLH
  • NHS GMS
  • Victorian Clinical Genetics Services
Phenotypes
  • Proteus syndrome, somatic 176920
Tags
mosaicism somatic
OMIM
164730
Clinvar variants
Variants in AKT1
Penetrance
None
Publications
Mode of Pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Panels with this gene

History Filter Activity

15 Aug 2019, Gel status: 1

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: akt1 has been classified as Red List (Low Evidence).

15 Aug 2019, Gel status: 1

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: akt1 has been classified as Red List (Low Evidence).

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source Wessex and West Midlands GLH was added to AKT1.

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source NHS GMS was added to AKT1.

11 Dec 2018, Gel status: 3

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

Arianna Tucci: Proteus syndrome is associated

27 Sep 2018, Gel status: 3

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: AKT1 were changed from to Proteus syndrome, somatic 176920

27 Sep 2018, Gel status: 3

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: AKT1 were set to 23992099; 21793738

27 Sep 2018, Gel status: 3

Set mode of pathogenicity

Sarah Leigh (Genomics England Curator)

Mode of pathogenicity for gene: AKT1 was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

27 Sep 2018, Gel status: 3

Set mode of inheritance

Sarah Leigh (Genomics England Curator)

Mode of inheritance for gene: AKT1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

27 Sep 2018, Gel status: 3

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: akt1 has been classified as Green List (High Evidence).

26 Sep 2018, Gel status: 2

Set mode of pathogenicity

Sarah Leigh (Genomics England Curator)

Mode of pathogenicity for gene: AKT1 was changed from None to None

26 Sep 2018, Gel status: 2

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: AKT1 were set to 23992099

17 Jul 2018, Gel status: 2

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: AKT1 were set to 23992099

16 Jul 2018, Gel status: 2

Set mode of inheritance

Sarah Leigh (Genomics England Curator)

Mode of inheritance for gene: AKT1 was changed from to Unknown

25 Jun 2018, Gel status: 2

Added New Source

Sarah Leigh (Genomics England Curator)

Expert Review Amber was added to AKT1. Panel: Genetic Epilepsy Syndromes

25 Jun 2018, Gel status: 1

Added New Source

Sarah Leigh (Genomics England Curator)

AKT1 was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services

25 Jun 2018, Gel status: 1

Created

Sarah Leigh (Genomics England Curator)

AKT1 was created by Sarah Leigh