Hereditary ataxia with onset in adulthood

Gene: TGM6

Green List (high evidence)

On Ox and Sheffield panels. SCA35.

Created: 27 Apr 2019, 7:39 p.m.

I don't know

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 Red

Created: 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.

I don't know

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