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  3. TTL
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Tubulinopathies

Gene: TTL

Amber List (moderate evidence)
TTL (tubulin tyrosine ligase)
EnsemblGeneIds (GRCh38): ENSG00000114999
EnsemblGeneIds (GRCh37): ENSG00000114999
OMIM: 608291, Gene2Phenotype
TTL is in 3 panels

1 review

Mark Cleghorn (Royal Melbourne Hospital)

I don't know

TTL
Valentina Serpieri, University of Pavia
ESHG talk 1/6/24

FAM1 (Italy)
2 affected sisters born to consanguineous Pakistani parents
GDD, spastic tetraparesis, optic atrophy, brain anomalies resembling tubulinopathies (dysplasia of corpus callosum, basal ganglia, brainstem)
WES: homozygous TTL:c.1013G>A; p.Cys338Tyr in both affected sisters

Via genematcher
5 more families (9 individuals) w similar phenotypes and biallelic variants in TTL

FAM2 (Egypt): homozygous p.Arg46Pro
FAM3 (Egypt): homozygous p.Arg46Pro
FAM4 (Australia): homozygous p.Gln183Arg
FAM5 (France): homozygous p.Trp147*
FAM6 (Saudi Arabia): homozygous p.His243Tyr

TTL KO mice: death soon after birth, no overt malformations, but defects in organisation of cerebral layers

Functional work on patient fibroblasts
FAM1 – reduced quantity of TTL protein compared to control on Western blot, decreased function of TTL protein (increase in detyrosinated tubulin) compared to controls – infer LoF as mechanism
FAM3 – mentioned but no details
FAM4– mentioned but no details
Sources: Other
Created: 4 Sep 2024, 2:22 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
complex neurodevelopmental disorder MONDO:0100038

Created: 4 Sep 2024, 2:22 a.m.

Panel version: 1.1

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • complex neurodevelopmental disorder MONDO:0100038
OMIM
608291
Clinvar variants
Variants in TTL
Penetrance
unknown
Panels with this gene

History Filter Activity

11 Sep 2024, Gel status: 2

Entity classified by Genomics England curator

Bryony Thompson (Royal Melbourne Hospital)

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

11 Sep 2024, Gel status: 2

Entity classified by Genomics England curator

Bryony Thompson (Royal Melbourne Hospital)

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

11 Sep 2024, Gel status: 2

Entity classified by Genomics England curator

Bryony Thompson (Royal Melbourne Hospital)

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

4 Sep 2024, Gel status: 0

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

Mark Cleghorn (Royal Melbourne Hospital)

gene: TTL was added gene: TTL was added to Tubulinopathies. Sources: Other Mode of inheritance for gene: TTL was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: TTL were set to complex neurodevelopmental disorder MONDO:0100038 Penetrance for gene: TTL were set to unknown Review for gene: TTL was set to AMBER