Hereditary ataxia with onset in adulthood
Gene: TGM6
On Ox and Sheffield panels. SCA35.Created: 27 Apr 2019, 7:39 p.m.
Downgraded rating from Amber to Red. As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene RedCreated: 1 Aug 2019, 3:43 p.m. | Last Modified: 1 Aug 2019, 3:43 p.m.
Panel Version: 1.188
Review and rating submitted by James Polke (Neurogenetics Laboratory, Institute of Neurology, London) on behalf of London North GLH for GMS Neurology specialist test group
Created: 27 Apr 2019, 8:55 p.m.
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.Created: 15 Apr 2019, 10:21 a.m.
Nearly all missense variants in HGMDPro are found within gnomAD, may at frequencies NOT consistent with AD variant. Functional evidence provided for a few variants is not convincing (PMID 28934387). In addition, one of the original variants has been reported with completely disparate phenotypes (ataxia versus leukaemia, PMIDs 21106500, 24755948). Gene very polymorphic within our cohort and gnomAD NOT consistent with either missense or truncating variants being pathogenic (Also PMID 24755948 suggests doubt on pathogenicity)Created: 15 Apr 2019, 10:06 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Spinocerebellar ataxia 35
Variants in this GENE are reported as part of current diagnostic practice
Source Expert Review Red was added to TGM6. Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Gene: tgm6 has been classified as Amber List (Moderate Evidence).
Source London North GMS was added to TGM6.
Added phenotypes Spinocerebellar ataxia 35 for gene: TGM6
Source NHS GMS was added to TGM6.
Source Wessex and West Midlands GLH was added to TGM6.
Checked panel against panel constituents. Ready to promote to version 1.
Phenotypes for gene: TGM6 were changed from Spinocerebellar ataxia 35 to Spinocerebellar ataxia 35, 613908
gene: TGM6 was added gene: TGM6 was added to Hereditary ataxia - adult onset. Sources: Hereditary ataxia v1.148,Expert Review Green Mode of inheritance for gene: TGM6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: TGM6 were set to Spinocerebellar ataxia 35