Mosaic brain disorders - deep sequencing

Gene: PTEN

Green List (high evidence)

PTEN (phosphatase and tensin homolog)
EnsemblGeneIds (GRCh38): ENSG00000171862
EnsemblGeneIds (GRCh37): ENSG00000171862
OMIM: 601728, Gene2Phenotype
PTEN is in 54 panels

5 reviews

Alexander Symon-Allen (Genetics Laboratory, Oxford UK)

Green List (high evidence)

Germline PTEN variant detected in fetus accompanied by a loss of heterozygosity in affected tissue. Further evidence that early post-zygotic 2nd hits are required for MCDs when a single germline hit is a LoF variant.
Created: 23 Jan 2026, 11:31 a.m. | Last Modified: 23 Jan 2026, 11:31 a.m.
Panel Version: 0.148

Mode of inheritance
Other

Phenotypes
Hemimegalencephaly

Publications

Sarah Leigh (Genomics England Curator)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Tom Cullup (Great Ormond Street Hospital)

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
macrocephaly/autism syndrome, OMIM:605309; focal cortical dysplasia (PMID: 17013611); PTEN harmatoma tumour syndrome/Cowden syndrome-1 (CWS1), OMIM:158350

Publications

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

Comment on classification of this gene: This gene should be rated as GREEN as there are sufficient cases (>3 unrelated cases) identified with variants in PTEN.

The gene-disease associations have already been reported in OMIM.

In addition to germline variants, two somatic variants of PTEN affecting a single patient with intractable epilepsy and hemimegalencephaly was reported in PMID:34048549.
Created: 21 Dec 2022, 4:28 p.m. | Last Modified: 21 Dec 2022, 4:28 p.m.
Panel Version: 0.44

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Cowden syndrome 1, OMIM:158350; Lhermitte-Duclos disease, OMIM:158350; Macrocephaly/autism syndrome, OMIM:605309

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

Eleanor Williams (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Created: 1 Feb 2023, 5:26 p.m. | Last Modified: 1 Feb 2023, 5:34 p.m.
Panel Version: 0.93
Review submitted on behalf of Dr Lara Menzies, Dr Wendy Jones, Dr Amy McTague. Mode of inheritance: AD, mosaic. Publications: For summary see Jansen et al 2015 and above MTOR summary papers.PTEN somatic mutations contribute to spectrum of cerebral overgrowth. Koboldt et al. Brain. 2021 Nov 29;144(10):2971-2978. doi: 10.1093/brain/awab173.PMID: 34048549 Mechanism: GOF (MTOR Pathway). Penetrance: variable penetrance.
Created: 21 Dec 2022, 12:16 p.m. | Last Modified: 21 Dec 2022, 12:16 p.m.
Panel Version: 0.2

Phenotypes
Macrocephaly and ID, Hemimegalencephaly. NB There are a number of assitional phenotypes associated with this gene that are not relevant for this particular clinical indication. Cortical Dysplasia, Complex Cerebral malformation

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • NHS GMS
  • Expert Review Green
  • Expert list
Phenotypes
  • Cowden syndrome 1, OMIM:158350
  • Lhermitte-Duclos disease, OMIM:158350
  • Macrocephaly/autism syndrome, OMIM:605309
Tags
somatic
OMIM
601728
Clinvar variants
Variants in PTEN
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

11 Oct 2023, Gel status: 3

Added New Source

Sarah Leigh (Genomics England Curator)

Source NHS GMS was added to PTEN.

31 May 2023, Gel status: 3

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: PTEN were set to 25722288; 34048549

22 Dec 2022, Gel status: 3

Set mode of pathogenicity

Arina Puzriakova (Genomics England Curator)

Mode of pathogenicity for gene: PTEN was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

21 Dec 2022, Gel status: 3

Added Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag somatic tag was added to gene: PTEN.

21 Dec 2022, Gel status: 3

Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

Phenotypes for gene: PTEN were changed from to Cowden syndrome 1, OMIM:158350; Lhermitte-Duclos disease, OMIM:158350; Macrocephaly/autism syndrome, OMIM:605309

21 Dec 2022, Gel status: 3

Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Publications for gene: PTEN were set to

21 Dec 2022, Gel status: 3

Set mode of inheritance

Achchuthan Shanmugasundram (Genomics England Curator)

Mode of inheritance for gene: PTEN was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

21 Dec 2022, Gel status: 3

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

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

21 Dec 2022, Gel status: 1

Created, Added New Source, Set mode of inheritance

Eleanor Williams (Genomics England Curator)

gene: PTEN was added gene: PTEN was added to Mosaic brain disorders. Sources: Expert list Mode of inheritance for gene: PTEN was set to