Skeletal Muscle Channelopathies
Gene: SCN4A
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
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
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.
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).
Phenotypes for SCN4A were set to Hyperkalemic periodic paralysis, type 2, 170500; Myasthenic syndrome, acetazolamide-responsive, 614198; Hypokalemic periodic paralysis, type 2, 613; Potassium-Aggravated Myotonia; Hyperkalemic Periodic Paralysis; Hypokalemic Periodic Paralysis; Thyrotoxic Periodic Paralysis, Susceptibility To, 2; Myotonia; Episodic weakness
Publications for SCN4A were set to 17395131; 15534250
Mode of inheritance for SCN4A was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene SCN4A were set to Hyperkalemic periodic paralysis, type 2, 170500; Myasthenic syndrome, acetazolamide-responsive, 614198; Hypokalemic periodic paralysis, type 2, 613; Potassium-Aggravated Myotonia; Hyperkalemic Periodic Paralysis; Hypokalemic Periodic Paralysis; Thyrotoxic Periodic Paralysis, Susceptibility To, 2;Myotonia; Episodic weakness
Mode of inheritance for SCN4A was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
This gene has been classified as Green List (High Evidence).
SCN4A was added to Skeletal Muscle Channelopathiespanel. Sources: Eligibility statement prior genetic testing
SCN4A was added to Skeletal Muscle Channelopathiespanel. Sources: UKGTN
Model of inheritance for gene SCN4A was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
SCN4A was added to Skeletal Muscle Channelopathiespanel. Sources: Illumina TruGenome Clinical Sequencing Services
SCN4A was added to Skeletal Muscle Channelopathiespanel. Sources: Radboud University Medical Center, Nijmegen