Skeletal Muscle Channelopathies

Gene: SCN4A

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

• 17395131
• 15534250

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

• 17395131
• 15534250

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)

Mostly missense mutations. two common path mutations: T704M and M1592V (periodic paralysis). A founder mutation (M1476I) in families with paramyotonia congenita.
Reduced penetrance.

Created: 10 Jan 2017, 3 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Hyperkalemic periodic paralysis, type 2; Hypokalemic periodic paralysis, type 2; Myotonia congenita, atypical, acetazolamide-responsive; Paramyotonia congenita

Publications

• 17395131
• 15534250

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, 2:47 p.m.

Comment on mode of inheritance: Confirmed on OMIM.

Created: 10 Jun 2016, 2:28 p.m.

Comment on list classification: This gene is in the genetic muscle channel diseases section in the UCLH National Hospital for Neurology and Neurosurgery & Institute of Neurology (NHNN) Neurogenetics genetic testing manual, for testing of Paramyotonia Congenita, one of the main skeletal muscle channelopathies.

Created: 10 Jun 2016, 2:26 p.m.