Adult onset neurodegenerative disorder
Gene: STUB1
The rating of this gene has been updated to Green and the mode of inheritance set to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.Created: 1 Feb 2023, 12:22 p.m. | Last Modified: 1 Feb 2023, 12:22 p.m.
Panel Version: 3.49
Added the Q3_22_rating tag in addition to the Q3_22_MOI tag.
The gene has been rating red in relation to Spinocerebellar ataxia, autosomal recessive 16 as the age of onset is mostly in the teenage years, not in adults.
However, there are several monoallelic cases relating to Spinocerebellar ataxia 48, which present in adulthood. However in some cases there is reduced penetrance or the STUB1 variant appears in conjunction with other variants (notably TBP_CAG expansions).
Waiting for GMS expert review of this gene to decide on the rating and mode of inheritance for this gene.Created: 12 Oct 2022, 2:24 p.m. | Last Modified: 12 Oct 2022, 2:24 p.m.
Panel Version: 2.289
Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. Numerous STUB1 variants have been reported in both Autosomal recessive spinocerebellar ataxia type 16, OMIM:615768 and Spinocerebellar ataxia 48, OMIM:618093.
PMIDs 34906452; 35493319 report digenic occurrence of heterozygous STUB1 variants, with TBP_CAG expansions of 41-46. They question the validy of Spinocerebellar ataxia 48 (OMIM:618093) as a condition and whether it should be included into Spinocerebellar ataxia 17 (OMIM:607136).Created: 13 Sep 2022, 11:39 a.m. | Last Modified: 13 Sep 2022, 11:39 a.m.
Panel Version: 2.287
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Further reports of dominant variants associated with ataxia +/- cognitive impairment (SCA48). Emerging evidence of digenic interaction with TBP (SCA17) 'intermediate' CAG expansions. LOF variants also associated with both recessive and dominant ataxia, further complicating interpretation.Created: 1 Sep 2022, 7:28 a.m. | Last Modified: 1 Sep 2022, 7:28 a.m.
Panel Version: 2.284
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Cerebellar Ataxia; Dementia
Publications
SCA48 - AD, only one family reported (Genis et al 2018) - amber. SCA16 - AR progressive neurologic disorder characterized by truncal and limb ataxia resulting in gait instability. Most patients have onset in the teenage years - red?Created: 2 Sep 2019, 4:06 p.m. | Last Modified: 2 Sep 2019, 4:06 p.m.
Panel Version: 1.99
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Spinocerebellar ataxia, autosomal recessive 16
Variable age at onsetCreated: 23 Jul 2019, 3:35 p.m. | Last Modified: 23 Jul 2019, 3:35 p.m.
Panel Version: 1.72
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Spinocerebellar ataxia, autosomal recessive 16, 615768
Publications
Variants in this GENE are reported as part of current diagnostic practice
As discussed with the GMS Neurology Specialist Test Group webex call 11th September 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene RedCreated: 20 Sep 2019, 4:19 p.m. | Last Modified: 20 Sep 2019, 4:19 p.m.
Panel Version: 1.106
Review and rating from Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group. All the green and amber, except for the genes with triplet repeats, were reviewed.Created: 2 Sep 2019, 4:46 p.m. | Last Modified: 2 Sep 2019, 4:46 p.m.
Panel Version: 1.101
Review and rating submitted by Nick Beauchamp (Sheffield Diagnostic genetics Service), on behalf of Yorkshire and North East GLH for GMS Neurology specialist test group.Created: 23 Jul 2019, 3:51 p.m. | Last Modified: 23 Jul 2019, 3:51 p.m.
Panel Version: 1.74
Review and rating submitted byJames Polke (North Bristol NHS Trust), unless specified in the review comment, on behalf of London North GLH for GMS Neurology specialist test group.Created: 23 Apr 2019, 5:35 p.m.
Tag Q3_22_rating was removed from gene: STUB1. Tag Q3_22_MOI was removed from gene: STUB1. Tag Q3_22_expert_review was removed from gene: STUB1.
Source Expert Review Green was added to STUB1. Mode of inheritance for gene STUB1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Rating Changed from Red List (low evidence) to Green List (high evidence)
Tag Q3_22_expert_review tag was added to gene: STUB1.
Mode of inheritance for gene: STUB1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Tag Q3_22_rating tag was added to gene: STUB1. Tag Q3_22_MOI tag was added to gene: STUB1.
Mode of inheritance for gene: STUB1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Tag Q3_22_rating was removed from gene: STUB1. Tag Q3_22_MOI was removed from gene: STUB1.
Tag Q3_22_rating tag was added to gene: STUB1.
Tag Q3_22_MOI tag was added to gene: STUB1.
Tag Q3_22_MOI was removed from gene: STUB1.
Tag Q3_22_MOI tag was added to gene: STUB1.
Phenotypes for gene: STUB1 were changed from Spinocerebellar ataxia, autosomal recessive 16 to Autosomal recessive spinocerebellar ataxia type 16, OMIM:615768; autosomal recessive spinocerebellar ataxia 16, MONDO:0014339; Spinocerebellar ataxia 48, OMIM:618093; spinocerebellar ataxia 48, MONDO:0032526
Publications for gene: STUB1 were set to 25592071; 30381368
Source Expert Review Red was added to STUB1. Rating Changed from Green List (high evidence) to Red List (low evidence)
Source Wessex and West Midlands GLH was added to STUB1.
Publications for gene STUB1 were changed from to 25592071; 30381368
Source Yorkshire and North East GLH was added to STUB1.
Source NHS GMS was added to STUB1.
Source London North GLH was added to STUB1.
Louise Daugherty: Comment on phenotypes: amended
gene: STUB1 was added gene: STUB1 was added to Neurodegenerative disorders - adult onset. Sources: Expert Review Green Mode of inheritance for gene: STUB1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: STUB1 were set to Spinocerebellar ataxia, autosomal recessive 16