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Intellectual disability

Gene: TBC1D20

Green List (high evidence)
TBC1D20 (TBC1 domain family member 20)
EnsemblGeneIds (GRCh38): ENSG00000125875
EnsemblGeneIds (GRCh37): ENSG00000125875
OMIM: 611663, Gene2Phenotype
TBC1D20 is in 7 panels

2 reviews

Rebecca Foulger (Genomics England curator)

Comment on list classification: Updated rating from Grey to Green. Gene added to panel and reviewed Green by Konstantinos Varvagiannis. 5 unrelated families (7 individuals) reported in PMID:24239381 (Liegel et al, 2013) with 5 different homozygous TBC1D20 loss of function variants, and all with profound or severe mental retardation and developmental delay (Supplementary table S4).
Created: 26 Feb 2019, 12:15 p.m.
Comment on mode of inheritance: Biallelic MOI supported by OMIM and PMID:24239381.
Created: 26 Feb 2019, 12:13 p.m.
Comment on publications: PMID:26063829 demonstrates biochemically that TBC1D20 is a regulator of RAB18 (associated with Warburg micro syndrome 3, 614222).
Created: 26 Feb 2019, 12:11 p.m.
Created: 26 Feb 2019, 12:11 p.m.

Panel version: 2.771

Konstantinos Varvagiannis (Other)

Green List (high evidence)

Biallelic pathogenic variants in TBC1D20 cause Warburg Micro syndrome 4 (MIM 615663).
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Liegel et al. (PMID: 24239381) report on 7 individuals from 5 unrelated families. ID was a universal feature along with opthalmological, endocrine and other neurological features of the disorder. Seizures were noted in 4 individuals from 2 families. Table S4 of this article provides clinical details on each subject.

All affected individuals were homozygous for LoF variants, private to each family. 3 nonsense variants, 1 frameshift one as well as an intragenic deletion (exons 2-8) were identified.

These subjects belonged to a cohort of 77 individuals with suspected Warburg Micro syndrome (WMS) or disorders of the same spectrum (eg. Martsolf syndrome).

Screening for TBC1D20 mutations in these individuals was performed after identification of a homozygous LoF Tbc1d20 mutation in blind sterile mice, presenting a phenotype somewhat similar to WMS (congenital cataracts and testicular anomalies).

Alternative causes of WMS (eg. pathogenic variants in RAB3GAP1, RAB3GAP2 and RAB18) had previously been excluded in this cohort.

The authors demonstrated aberrant lipid droplet formation in embryonic fibroblasts from blind sterile mice as well as in fibroblasts from individuals with a diagnosis of WMS due to mutations in either of TBC1D20, RAB18 and RAB3GAP1.
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TBC1D20 is included in the DD panel of G2P, associated with Warburg micro syndrome 4 (Disease confidence: probable / ID among the phenotypes assigned to this entry).

This gene is included in gene panels for ID offered by different diagnostic laboratories (incl. Radboudumc).
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As a result, TBC1D20 can be considered for inclusion in the ID panel as green (or amber).
Sources: Literature, Radboud University Medical Center, Nijmegen
Created: 1 Jan 2019, 11:51 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Warburg Micro syndrome 4 (MIM 615663)

Publications

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

Created: 1 Jan 2019, 11:51 p.m.

Panel version: 2.588

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
Phenotypes
  • Warburg micro syndrome 4, 615663
  • mental retardation
  • developmental delay
OMIM
611663
Clinvar variants
Variants in TBC1D20
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

26 Feb 2019, Gel status: 3

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: tbc1d20 has been classified as Green List (High Evidence).

26 Feb 2019, Gel status: 0

Set mode of inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for gene: TBC1D20 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal

26 Feb 2019, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: TBC1D20 were set to 24239381; 26063829

26 Feb 2019, Gel status: 0

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: TBC1D20 were changed from Warburg Micro syndrome 4 (MIM 615663) to Warburg micro syndrome 4, 615663; mental retardation; developmental delay

1 Jan 2019, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance

Konstantinos Varvagiannis (Other)

gene: TBC1D20 was added gene: TBC1D20 was added to Intellectual disability. Sources: Literature,Radboud University Medical Center, Nijmegen Mode of inheritance for gene: TBC1D20 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TBC1D20 were set to 24239381; 26063829 Phenotypes for gene: TBC1D20 were set to Warburg Micro syndrome 4 (MIM 615663) Penetrance for gene: TBC1D20 were set to Complete Review for gene: TBC1D20 was set to GREEN gene: TBC1D20 was marked as current diagnostic