Skeletal Muscle Channelopathies

Gene: CACNA1S

Green List (high evidence)

CACNA1S (calcium voltage-gated channel subunit alpha1 S)
EnsemblGeneIds (GRCh38): ENSG00000081248
EnsemblGeneIds (GRCh37): ENSG00000081248
OMIM: 114208, Gene2Phenotype
CACNA1S is in 9 panels

5 reviews

Fowzan ALKURAYA (King Faisal Specialist Hospital and Research Center)

Green List (high evidence)

Reported mutations tend to be missense rather than LOF. PLI is very low in ExAC, which also suggests a disease mechanism other than LOF or haploinsufficiency.
Created: 22 Feb 2017, 3:38 p.m.

Publications

Mode of pathogenicity
Other - please provide details in the comments

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

Fowzan ALKURAYA (King Faisal Specialist Hospital and Research Center)

Green List (high evidence)

Reported mutations tend to be missense rather than LOF. PLI is very low in ExAC, which also suggests a disease mechanism other than LOF or haploinsufficiency.
Created: 22 Feb 2017, 3:31 p.m.

Publications

Mode of pathogenicity
Other - please provide details in the comments

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

Arianna Tucci (Genomics England Curator)

Arianna Tucci (Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square)

Green List (high evidence)

The R1239H R528H are commonly found pathogenic mutations of the CACNA1S gene.
Hypokalemic periodic paralysis shows markedly reduced penetrance in females, although penetrance is 100% in males.
Can be treated (dietary intervention, oral potassium supplementation and acetazolamide treatment may be beneficial in some cases).
Created: 10 Jan 2017, 11:11 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
hypokalemic periodic paralysis type 1

Publications

Ellen McDonagh (Genomics England Curator)

Is on the Muscle Channel NGS Panel in the UCLH National Hospital for Neurology and Neurosurgery & Institute of Neurology (NHNN) Neurogenetics genetic testing manual.
Created: 10 Jun 2016, 2:42 p.m.
Comment on list classification: This gene is tested for Hypokalemic periodic paralysis in the UCLH National Hospital for Neurology and Neurosurgery & Institute of Neurology (NHNN) Neurogenetics genetic testing manual.
Created: 10 Jun 2016, 2:40 p.m.

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • Eligibility statement prior genetic testing
  • UKGTN
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Hypokalemic periodic paralysis, type 1, 170400
Tags
treatable
OMIM
114208
Clinvar variants
Variants in CACNA1S
Penetrance
Incomplete
Publications
Panels with this gene

History Filter Activity

22 Feb 2017, Gel status: 4

panel promoted to version 1

Arianna Tucci (Genomics England Curator)

Promoted 22/02/2017 after curation discussion and further review with members of the Genomics England curation team.

21 Jan 2017, Gel status: 4

Gene classified by Genomics England curator

Arianna Tucci (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

13 Jan 2017, Gel status: 3

Set Mode of Inheritance

Arianna Tucci (Genomics England Curator)

Mode of inheritance for CACNA1S was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

13 Jan 2017, Gel status: 3

Set Phenotypes

Arianna Tucci (Genomics England Curator)

Phenotypes for CACNA1S were set to Hypokalemic periodic paralysis, type 1, 170400

13 Jan 2017, Gel status: 3

Gene classified by Genomics England curator

Arianna Tucci (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

13 Jan 2017, Gel status: 4

Set Phenotypes

Arianna Tucci (Genomics England Curator)

Phenotypes for CACNA1S were set to Hypokalemic periodic paralysis, type 1, 170400; {Malignant hyperthermia susceptibility 5}, 601887; {Thyrotoxic periodic paralysis, susceptibility to, 1}, 188580; Hypokalemic Periodic Paralysis; Andersen Cardiodysrhythmic Periodic Paralysis; Episodic weakness

13 Jan 2017, Gel status: 4

Set publications

Arianna Tucci (Genomics England Curator)

Publications for CACNA1S were set to 15534250; 18835861

10 Jun 2016, Gel status: 4

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

12 Aug 2015, Gel status: 3

Added New Source

Ellen McDonagh (Genomics England Curator)

CACNA1S was added to Skeletal Muscle Channelopathiespanel. Sources: Eligibility statement prior genetic testing

7 Aug 2015, Gel status: 3

Added New Source

Eik Haraldsdottir (Genomics England)

CACNA1S was added to Skeletal Muscle Channelopathiespanel. Sources: UKGTN

7 Aug 2015, Gel status: 2

Set Mode of Inheritance

Eik Haraldsdottir (Genomics England)

Model of inheritance for gene CACNA1S was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

7 Aug 2015, Gel status: 2

Added New Source

Eik Haraldsdottir (Genomics England)

CACNA1S was added to Skeletal Muscle Channelopathiespanel. Sources: Illumina TruGenome Clinical Sequencing Services

7 Aug 2015, Gel status: 1

Added New Source

Eik Haraldsdottir (Genomics England)

CACNA1S was added to Skeletal Muscle Channelopathiespanel. Sources: Radboud University Medical Center, Nijmegen