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Intellectual disability

Gene: TBC1D7

Green List (high evidence)
TBC1D7 (TBC1 domain family member 7)
EnsemblGeneIds (GRCh38): ENSG00000145979
EnsemblGeneIds (GRCh37): ENSG00000145979
OMIM: 612655, Gene2Phenotype
TBC1D7 is in 4 panels

5 reviews

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Created: 24 Feb 2025, 6:15 p.m. | Last Modified: 24 Feb 2025, 6:15 p.m.
Panel Version: 8.97

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Created: 24 Feb 2025, 6:15 p.m.
Last Modified: 24 Feb 2025, 6:15 p.m.
Panel version: 8.97

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

Comment on list classification: As reviewed by Frances Elmslie, PMID:36669495 reported an additional case with compound heterozygous variants (identified via trio RNA-Seq) and presenting with a neurodevelopmental disorder involving mild intellectual disability.

Hence, this gene can be promoted to green rating with the current evidence (three unrelated cases and functional studies) in the next GMS update.
Created: 11 Jul 2024, 4:46 p.m. | Last Modified: 11 Jul 2024, 4:46 p.m.
Panel Version: 6.52

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

Created: 11 Jul 2024, 4:41 p.m.
Last Modified: 11 Jul 2024, 4:41 p.m.
Panel version: 6.50

Frances Elmslie (South West Thames Regional genetics service)

Green List (high evidence)

Two papers from 2013 and 2014 (Capo-Chichi et al and Alfaiz et al) described two separate consanguineous families with homozygous variants in this gene. Both provided functional evidence for pathogenicity demonstrating constitutive activation of the mTORC1 complex. In both papers, 2 children were affected and the variants segregated with the phenotype. The individuals described in the second paper had a more complex phenotype which could potentially have an alternative cause. A further paper of unsolved patients with neurodevelopmental disorders identified compound heterozygous variants in another individual with macrocephaly and ID (Dekker et al 2023), again providing functional evidence for causation. A knock out mouse model recapitulated the human phenotype (Schrotter et al 2022).
Created: 6 Jul 2024, 9:58 a.m. | Last Modified: 6 Jul 2024, 9:58 a.m.
Panel Version: 6.50

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Macrocephaly; intellectual disability; megalencephaly

Publications

Created: 6 Jul 2024, 9:58 a.m.
Last Modified: 6 Jul 2024, 9:58 a.m.
Panel version: 6.50

Rebecca Foulger (Genomics England curator)

Added watchlist tag.
Created: 26 Feb 2019, 12:34 p.m.
Comment on list classification: Updated rating from Grey to Amber. Gene added to panel and reviewed Amber by Konstantinos Varvagiannis. Currently only 2 unrelated ID cases from 2 publications (PMID:23687350 Capo-Chichi et al 2013 and PMID:24515783 Alfaiz et al 2014). TBC1D7 is not currently associated with a phenotype in DD-Gene2Phenotype. Therefore rated Amber awaiting further cases.
Created: 26 Feb 2019, 12:33 p.m.
Created: 26 Feb 2019, 12:33 p.m.

Panel version: 2.774

Konstantinos Varvagiannis (Other)

I don't know

PMID 23687350 reports 2 individuals from a consanguineous family with intellectual disability and megalencephaly. Both individuals were homozygous for a frameshift variant in TBC1D7. A further report (PMID 24515783) describes two sisters born to Italian parents from distant villages, homozygous for a TBC1D7 frameshift variant. Both children presented a similar phenotype consisting of mild intellectual disability, macrocrania, patellar dislocation as well as celiac disease.
Created: 13 Aug 2018, 10:20 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Macrocephaly/megalencephaly syndrome, autosomal recessive, 248000

Publications

Created: 13 Aug 2018, 10:20 p.m.

Panel version: 2.379

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • NHS GMS
Phenotypes
  • Macrocephaly/megalencephaly syndrome, autosomal recessive, OMIM:248000
OMIM
612655
Clinvar variants
Variants in TBC1D7
Penetrance
unknown
Publications
Panels with this gene

History Filter Activity

25 Feb 2025, Gel status: 3

Removed Tag, Removed Tag

Sarah Leigh (Genomics England Curator)

Tag Q3_24_promote_green was removed from gene: TBC1D7. Tag Q3_24_NHS_review was removed from gene: TBC1D7.

24 Feb 2025, Gel status: 3

Added New Source, Added New Source, Status Update

Sarah Leigh (Genomics England Curator)

Source NHS GMS was added to TBC1D7. Source Expert Review Green was added to TBC1D7. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

11 Jul 2024, Gel status: 2

Removed Tag, Added Tag, Added Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag watchlist was removed from gene: TBC1D7. Tag Q3_24_promote_green tag was added to gene: TBC1D7. Tag Q3_24_NHS_review tag was added to gene: TBC1D7.

11 Jul 2024, Gel status: 2

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

Gene: tbc1d7 has been classified as Amber List (Moderate Evidence).

11 Jul 2024, Gel status: 2

Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Publications for gene: TBC1D7 were set to PMID: 23687350; 24515783

22 Dec 2022, Gel status: 2

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: TBC1D7 were changed from intellectual disability; macrocephaly; megalencephaly to Macrocephaly/megalencephaly syndrome, autosomal recessive, OMIM:248000

26 Feb 2019, Gel status: 2

Added Tag

Rebecca Foulger (Genomics England curator)

Tag watchlist tag was added to gene: TBC1D7.

26 Feb 2019, Gel status: 2

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: tbc1d7 has been classified as Amber List (Moderate Evidence).

12 Aug 2018, Gel status: 0

Added New Source

Konstantinos Varvagiannis (Other)

TBC1D7 was added to Intellectual disability panel. Sources: Literature

12 Aug 2018, Gel status: 0

Created

Konstantinos Varvagiannis (Other)

TBC1D7 was created by Konstantinos Varvagiannis