Genes in panel

Hereditary neuropathy

Gene: TRPA1

Green List (high evidence)

TRPA1 (transient receptor potential cation channel subfamily A member 1)
EnsemblGeneIds (GRCh38): ENSG00000104321
EnsemblGeneIds (GRCh37): ENSG00000104321
OMIM: 604775, Gene2Phenotype
TRPA1 is in 4 panels

3 reviews

Tracy Lester (Genetics laboratory, Oxford UK)

I don't know

There are just 2 reports in the literature with variants in this gene. A missense variant has been associated with a neurologic disorder characterised by onset in infancy of episodic debilitating upper body pain triggered by fasting, cold and physical stress. Pathogenicity has been confirmed through segregation and functional analysis that shows a gain of function.

A truncating variant has been associated with carbamazepine responsive cramp-fasciculation syndrome in a father and son (PMID: 28436534). There is no other evidence to support pathogenicity of this variant and the variant has been seen heterozygously in 20 individuals in gnomad. The pLI for this gene is zero - suggesting LOF variants are tolerated.

As there is only one confirmed report in the literature this gene does not meet the criteria to be green and should be listed as amber.
Created: 15 Jun 2020, 12:11 p.m. | Last Modified: 15 Jun 2020, 12:11 p.m.
Panel Version: 1.368

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
episodic debilitating upper body pain triggered by fasting, cold and physical stress

Publications

Louise Daugherty (Genomics England Curator)

Green List (high evidence)

The Neurology Specialist Test Group agreed that this gene was recommended for the WGS panel based on a broader phenotype view to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP. This panel includes conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation. This panel as going to be used for R78, but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy and as a result a new panel was created https://panelapp.genomicsengland.co.uk/panels/846/ for this purpose.
Created: 7 Dec 2019, 6:08 p.m. | Last Modified: 7 Dec 2019, 6:08 p.m.
Panel Version: 1.352
Rating and review submitted on behalf of James Polke (Neurogenetics Laboratory,Institute of Neurology, London), on behalf of London North GLH for GMS Neurology specialist test group.
Created: 9 May 2019, 5 p.m.

James Polke (Neurogenetics Laboratory, Institute of Neurology, London)

Green List (high evidence)

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
Phenotypes
  • Episodic pain syndrome, familial, 1, 615040
OMIM
604775
Clinvar variants
Variants in TRPA1
Penetrance
None
Panels with this gene

History Filter Activity

7 Dec 2019, Gel status: 3

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: TRPA1 were changed from to Episodic pain syndrome, familial, 1, 615040

7 Dec 2019, Gel status: 3

Set mode of inheritance

Louise Daugherty (Genomics England Curator)

Mode of inheritance for gene: TRPA1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

7 Dec 2019, Gel status: 3

Added New Source, Status Update

Louise Daugherty (Genomics England Curator)

Source Expert Review Green was added to TRPA1. Rating Changed from Red List (low evidence) to Green List (high evidence)

29 Apr 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to TRPA1.

29 Apr 2019, Gel status: 1

Created, Added New Source, Set mode of inheritance

Louise Daugherty (Genomics England Curator)

gene: TRPA1 was added gene: TRPA1 was added to Hereditary neuropathy. Sources: London North GLH Mode of inheritance for gene: TRPA1 was set to