Skeletal Muscle Channelopathies
Gene: CACNA1SComment on mode of inheritance: Changing MOI from "MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted" to "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" based on the review by Eleanor Williams for the same gene on the "Skeletal muscle channelopathy" panel:
"PMID: 28012042 - Shartner et al 2017 - report 11 individuals with congenital myopathy from 7 unrelated families (Caucasian, Argentinean, or Vietnamese) and variants in CACNA1S identified through exome sequencing. The s from origin were included in this study. There were 3 sporadic cases (2 compound het, 1 het), 2 families with dominant inheritance, and 2 families with recessive inheritance . 10 different variants were identified.
Eleanor Williams (Genomics England Curator), 17 Mar 2021"Created: 13 Jul 2021, 1:25 p.m. | Last Modified: 13 Jul 2021, 1:25 p.m.
Panel Version: 1.33
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
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
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
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.
Publications for gene: CACNA1S were set to 15534250; 18835861
Mode of inheritance for gene: CACNA1S was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Promoted 22/02/2017 after curation discussion and further review with members of the Genomics England curation team.
This gene has been classified as Green List (High Evidence).
Mode of inheritance for CACNA1S was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for CACNA1S were set to Hypokalemic periodic paralysis, type 1, 170400
This gene has been classified as Green List (High Evidence).
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
Publications for CACNA1S were set to 15534250; 18835861
This gene has been classified as Green List (High Evidence).
CACNA1S was added to Skeletal Muscle Channelopathiespanel. Sources: Eligibility statement prior genetic testing
CACNA1S was added to Skeletal Muscle Channelopathiespanel. Sources: UKGTN
Model of inheritance for gene CACNA1S was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
CACNA1S was added to Skeletal Muscle Channelopathiespanel. Sources: Illumina TruGenome Clinical Sequencing Services
CACNA1S was added to Skeletal Muscle Channelopathiespanel. Sources: Radboud University Medical Center, Nijmegen