Skeletal Muscle Channelopathies

Gene: CACNA1S

Comment 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

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

• 15534250
• 18835861

Mode of pathogenicity
Other - please provide details in the comments

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

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

• 15534250
• 18835861

Mode of pathogenicity
Other - please provide details in the comments

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

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

• 15534250
• 18835861

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.