Skeletal muscle channelopathy

Gene: CACNA1A

Green List (high evidence)

CACNA1A (calcium voltage-gated channel subunit alpha1 A)
EnsemblGeneIds (GRCh38): ENSG00000141837
EnsemblGeneIds (GRCh37): ENSG00000141837
OMIM: 601011, Gene2Phenotype
CACNA1A is in 26 panels

4 reviews

Eleanor Williams (Genomics England Curator)

Red List (low evidence)

Comment on list classification: Leaving rating as Green but with a recommendation for review by the GMS test evaluation group as to suitability for this panel. As reported by Zornitza Stark variants in this gene appear to be associated with brain channelopathies rather than skeletal muscle.
Created: 9 Jun 2021, 9:49 a.m. | Last Modified: 20 Jul 2021, 2:01 p.m.
Panel Version: 1.31
Review of case reports following expert review by Zornitiza Stark

PMID: 29442233 - Park et al 2018 - report of a patient with episodic ataxia 2 presenting with periodic paralysis and a de novo frameshift mutation in CACNA1A. The patient exhibited oculomotor signs of cerebellar dysfunction.

PMID: 17575281 - Jen et al 2007 - review of cases associated with CACNA1A variants relating to Familial hemiplegic migraine, Episodic ataxia and Spinocerebellar ataxia type 6.

PMID: 8734765 - Terwindt et al 1996 - 3 families with familial hemiplegic migraine linked to chr 19. Abstract only accessed.
Created: 9 Jun 2021, 9:47 a.m. | Last Modified: 9 Jun 2021, 9:47 a.m.
Panel Version: 1.24

Zornitza Stark (Australian Genomics)

Red List (low evidence)

Well established gene-disease association but predominantly a brain rather than skeletal muscle channelopathy.
Created: 20 Aug 2020, 8:45 a.m. | Last Modified: 20 Aug 2020, 8:45 a.m.
Panel Version: 1.4

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Episodic ataxia, type 2, MIM# 108500

Louise Daugherty (Genomics England Curator)

I don't know

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, 4:57 p.m.

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

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Episodic ataxia 2 with periodic paralysis; Episodic ataxia, type 2, 108500; Migraine, familial hemiplegic, 1, 141500; Epileptic encephalopathy, early infantile, 42, 617106

Publications

  • Park et al 2018 Acta Neurologica Belgica 118, 137-139 PMID: 29442233. Jen et al 2007 Brain 130, 2484-93 PMID: 17575281. Terwindt et al 1996 Cephalalgia 16, 153-5 PMID: 8734765

Variants in this GENE are reported as part of current diagnostic practice

History Filter Activity

8 Nov 2021, Gel status: 3

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: CACNA1A were changed from Episodic ataxia 2 with periodic paralysis; Epileptic encephalopathy, early infantile, 42 OMIM:617106; Migraine, familial hemiplegic, 1 OMIM:141500; Episodic ataxia, type 2 OMIM:108500 to Episodic ataxia, type 2, OMIM:108500; Migraine, familial hemiplegic, 1, OMIM:141500; Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia, OMIM:141500

20 Jul 2021, Gel status: 3

Removed Tag

Eleanor Williams (Genomics England Curator)

Tag Q2_21_rating was removed from gene: CACNA1A.

9 Jun 2021, Gel status: 3

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: cacna1a has been classified as Green List (High Evidence).

9 Jun 2021, Gel status: 3

Added Tag, Added Tag

Eleanor Williams (Genomics England Curator)

Tag Q2_21_rating tag was added to gene: CACNA1A. Tag Q2_21_phenotype tag was added to gene: CACNA1A.

15 Mar 2021, Gel status: 3

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: CACNA1A were changed from Episodic ataxia 2 with periodic paralysis; Epileptic encephalopathy, early infantile, 42, 617106; Migraine, familial hemiplegic, 1, 141500; Episodic ataxia, type 2, 108500 to Episodic ataxia 2 with periodic paralysis; Epileptic encephalopathy, early infantile, 42 OMIM:617106; Migraine, familial hemiplegic, 1 OMIM:141500; Episodic ataxia, type 2 OMIM:108500

25 Oct 2019, Gel status: 3

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene CACNA1A were changed from to 29442233; 8734765; 17575281

25 Oct 2019, Gel status: 3

Set mode of inheritance, Set Phenotypes

Louise Daugherty (Genomics England Curator)

Mode of inheritance for gene CACNA1A was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Added phenotypes Episodic ataxia 2 with periodic paralysis; Epileptic encephalopathy, early infantile, 42, 617106; Migraine, familial hemiplegic, 1, 141500; Episodic ataxia, type 2, 108500 for gene: CACNA1A

28 Apr 2019, Gel status: 3

Added New Source, Status Update

Louise Daugherty (Genomics England Curator)

Source Expert Review Green was added to CACNA1A. Rating Changed from Red List (low evidence) to Green List (high evidence)

28 Apr 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to CACNA1A.

28 Apr 2019, Gel status: 1

Created, Added New Source, Set mode of inheritance

Louise Daugherty (Genomics England Curator)

gene: CACNA1A was added gene: CACNA1A was added to Myotonia congenita. Sources: London North GLH Mode of inheritance for gene: CACNA1A was set to