Skeletal Muscle Channelopathies eligibility statement: Skeletal Muscle Channelopathies inclusion criteria (29575) - Episodic flaccid paralysis or weakness and/or myotonia - May develop progressive, usually proximal, weakness - Electrophysiology including long and short exercise testing - Intra-attack potassium documented whenever possible - Normal renal function and thyroid function Skeletal Muscle Channelopathies exclusion criteria (29575) - Primary renal or endocrine problem that may be causative - Associated loss of consciousness with attacks Prior genetic testing guidance (29575) - Results should have been reviewed for all genetic tests undertaken, including disease-relevant genes in exome sequencing data. The patient is not eligible if they have a molecular diagnosis for their condition. - Genetic testing should continue according to routine local practice for this phenotype regardless of recruitment to the project; results of these tests must be submitted via the ‘Genetic investigations’ section of the data capture tool to allow comparison of WGS with current standard testing. PLEASE NOTE: The sensitivity of WGS compared to current diagnostic genetic testing has not yet been established. It is therefore important that tests which are clinically indicated under local standard practice continue to be carried out. Skeletal Muscle Channelopathies prior genetic testing genes (29575) Testing of the following genes should be carried out PRIOR TO RECRUITMENT where this is in line with current local practice: - Myotonia: DMPK, CNBP, SCN4A, CLCN1 (including MLPA) - Episodic weakness: CACNA1S, SCN4A, KCNJ2 Closing statement (29575) These requirements will be kept under continual review during the main programme and may be subject to change.
Ellen McDonagh (Genomics England Curator)
Group: Other
Workplace: Other
Arianna Tucci (Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square)
Group: Other
Workplace: Other
Sarah Leigh (Genomics England Curator)
Group: Other
Workplace: Other
Alice Gardham (Genomics England)
Group: Other
Workplace: Other
Louise Daugherty (Genomics England Curator)
Group: Other
Workplace: Other
Arianna Tucci (Genomics England Curator)
Group: Other
Workplace: Other
Fowzan ALKURAYA (King Faisal Specialist Hospital and Research Center)
Group: Other
Workplace: Other
Eleanor Williams (Genomics England Curator)
Group: Other
Workplace: Other
Ivone Leong (Genomics England Curator)
Group: Other
Workplace: Other
Arina Puzriakova (Genomics England Curator)
Group: Other
Workplace: Other
| List | Entity | Reviews | Mode of inheritance | Details | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Green List (high evidence) |
ADCY5 |
4 reviews3 green |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
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| Green List (high evidence) |
ATP1A2 |
2 reviews1 green |
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown |
Sources
Phenotypes
Tags |
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| Green List (high evidence) |
ATP2A1 |
4 reviews3 green |
BIALLELIC, autosomal or pseudoautosomal |
Sources
Phenotypes
Tags |
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| Green List (high evidence) |
CACNA1A |
6 reviews3 red |
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown |
Sources
Phenotypes
Tags |
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| Green List (high evidence) |
CACNA1S |
6 reviews3 green |
BOTH monoallelic and biallelic, autosomal or pseudoautosomal |
Sources
Phenotypes
Tags |
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| Green List (high evidence) |
CLCN1 |
5 reviews3 green |
BOTH monoallelic and biallelic, autosomal or pseudoautosomal |
Sources
Phenotypes
Tags |
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| Green List (high evidence) |
CNBP_CCTGSTR |
4 reviews2 green 1 red |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
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| Green List (high evidence) |
DMPK_CTGSTR |
3 reviews2 green |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
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| Green List (high evidence) |
KCNA1 |
5 reviews2 green 1 red |
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown |
Sources
Phenotypes
Tags |
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| Green List (high evidence) |
KCNJ2 |
5 reviews3 green |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
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| Green List (high evidence) |
MT-ATP6 |
1 review1 green |
MITOCHONDRIAL |
Sources
Tags |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Green List (high evidence) |
MT-ATP8 |
1 review1 green |
MITOCHONDRIAL |
Sources
Tags |
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| Green List (high evidence) |
PYGM |
2 reviews |
BIALLELIC, autosomal or pseudoautosomal |
Sources
Phenotypes
Tags |
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| Green List (high evidence) |
RYR1 |
1 review1 green |
BOTH monoallelic and biallelic, autosomal or pseudoautosomal |
Sources
Tags |
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| Green List (high evidence) |
SCN4A |
4 reviews3 green |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
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| Green List (high evidence) |
SLC1A3 |
6 reviews3 red |
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown |
Sources
Phenotypes
Tags |
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| Green List (high evidence) |
SLC2A1 |
2 reviews1 green |
BOTH monoallelic and biallelic, autosomal or pseudoautosomal |
Sources
Phenotypes
Tags |
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| Amber List (moderate evidence) |
KCNJ5 |
2 reviews1 green |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Tags |
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| Red List (low evidence) |
CACNB4 |
5 reviews3 red |
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown |
Sources
Phenotypes
Tags |
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| Red List (low evidence) |
CNBP |
7 reviews1 red |
Other |
Sources
Phenotypes
Tags |
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| Red List (low evidence) |
DMPK |
6 reviews2 green 1 red |
Other |
Sources
Phenotypes
Tags |
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| Red List (low evidence) |
HSPG2 |
1 review1 green |
BIALLELIC, autosomal or pseudoautosomal |
Sources
Phenotypes
Tags |
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| Red List (low evidence) |
KCNJ18 |
6 reviews1 green 2 red |
Not set |
Sources
Phenotypes
Tags |
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| Red List (low evidence) |
KCNQ2 |
6 reviews3 red |
Not set |
Sources
Phenotypes
Tags |
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Promoted 22/02/2017 after curation discussion and further review with members of the Genomics England curation team.