Batten-Turner congenital myopathy

Summary

Batten-Turner congenital myopathy (MONDO:0100468) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 99

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Batten-Turner congenital myopathy
Mondo ID	MONDO:0100468
OMIM	255300
DOID	DOID:0081335
UMLS	C0027127
MedGen	10158
GARD	0026232
Is cancer (heuristic)	no

Data availability: 99 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › skeletal muscle disorder › myopathy › congenital myopathy › Batten-Turner congenital myopathy

Related subtypes (53): Ullrich congenital muscular dystrophy, congenital structural myopathy, Bethlem myopathy, MYH7-related skeletal myopathy, tubular aggregate myopathy, cylindrical spirals myopathy, congenital myopathy 7A, myosin storage, autosomal dominant, intellectual disability-myopathy-short stature-endocrine defect syndrome, myopathy, myosin storage, autosomal recessive, Bailey-Bloch congenital myopathy, fingerprint body myopathy, myopathy, proximal, and ophthalmoplegia, Compton-North congenital myopathy, MEGF10-related myopathy, fetal akinesia-cerebral and retinal hemorrhage syndrome, Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome, severe hypotonia-psychomotor developmental delay-strabismus-cardiac septal defect syndrome, myopathy with hexagonally cross-linked tubular arrays, benign Samaritan congenital myopathy, congenital generalized hypercontractile muscle stiffness syndrome, hyaline body myopathy, centronuclear myopathy, reducing body myopathy, myopathy, congenital, with tremor, myopathy, congenital, progressive, with scoliosis, myopathy, congenital, with structured cores and z-line abnormalities, myopathy, congenital, with respiratory insufficiency and bone fractures, myopathy, congenital proximal, with minicore lesions, myopathy, congenital, with diaphragmatic defects, respiratory insufficiency, and dysmorphic facies, congenital myopathy with reduced type 2 muscle fibers, alpha-actinopathy, SELENON-related myopathy, TPM3-related myopathy, SCN4A-related myopathy, autosomal recessive, RYR1-related myopathy, TTN-related myopathy, TPM2-related myopathy, TOR1AIP1-related myopathy, congenital myopathy 11, congenital myopathy 15, congenital myopathy 18, congenital myopathy 10b, mild variant, congenital myopathy 2b, severe infantile, autosomal recessive, congenital myopathy 2c, severe infantile, autosomal dominant, congenital myopathy 20, congenital myopathy 21 with early respiratory failure, congenital myopathy 22A, classic, congenital myopathy 22B, severe fetal, congenital myopathy 25, congenital myopathy 26, congenital myopathy 27, congenital myopathy 28 with rigid spine, congenital myopathy 29 with contractures

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

99 retrieved; paginated sample, class counts are floors:

29 conflicting classifications of pathogenicity, 21 uncertain significance, 16 benign/likely benign, 10 likely benign, 8 pathogenic, 7 pathogenic/likely pathogenic, 6 benign, 1 likely pathogenic, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
17532	NM_000083.3(CLCN1):c.689G>A (p.Gly230Glu)	CLCN1	Pathogenic	criteria provided, multiple submitters, no conflicts
17537	NM_000083.3(CLCN1):c.1439C>T (p.Pro480Leu)	CLCN1	Pathogenic	criteria provided, single submitter
17538	NM_000083.3(CLCN1):c.1655A>G (p.Gln552Arg)	CLCN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17539	NM_000083.3(CLCN1):c.870C>G (p.Ile290Met)	CLCN1	Pathogenic	criteria provided, multiple submitters, no conflicts
17542	NM_000083.3(CLCN1):c.950G>A (p.Arg317Gln)	CLCN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17545	NM_000083.3(CLCN1):c.2680C>T (p.Arg894Ter)	CLCN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17546	NM_000083.3(CLCN1):c.382A>G (p.Met128Val)	CLCN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
208084	NM_000083.3(CLCN1):c.1649C>T (p.Thr550Met)	CLCN1	Pathogenic	criteria provided, multiple submitters, no conflicts
21040	NM_000083.3(CLCN1):c.1592C>T (p.Ala531Val)	CLCN1	Pathogenic	criteria provided, multiple submitters, no conflicts
21050	NM_000083.3(CLCN1):c.920T>C (p.Phe307Ser)	CLCN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
21051	NM_000083.3(CLCN1):c.929C>T (p.Thr310Met)	CLCN1	Pathogenic	criteria provided, multiple submitters, no conflicts
265646	NM_000083.3(CLCN1):c.774+1G>A	CLCN1	Pathogenic	criteria provided, multiple submitters, no conflicts
279778	NM_000083.3(CLCN1):c.1437_1450del (p.Pro480fs)	CLCN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
280101	NM_000083.3(CLCN1):c.1453A>G (p.Met485Val)	CLCN1	Pathogenic	criteria provided, multiple submitters, no conflicts
664036	NM_000083.3(CLCN1):c.762C>G (p.Cys254Trp)	CLCN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1202581	NM_000083.3(CLCN1):c.1393G>T (p.Val465Phe)	CLCN1	Likely pathogenic	criteria provided, single submitter
208083	NM_000083.3(CLCN1):c.1283T>C (p.Phe428Ser)	CLCN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
252462	NM_000083.3(CLCN1):c.2284+5C>T	CLCN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
252463	NM_000083.3(CLCN1):c.899G>A (p.Arg300Gln)	CLCN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
289005	NM_000083.3(CLCN1):c.1392C>T (p.Phe464=)	CLCN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
359091	NM_000083.3(CLCN1):c.86A>C (p.His29Pro)	CLCN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
359092	NM_000083.3(CLCN1):c.156C>T (p.Pro52=)	CLCN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
359095	NM_000083.3(CLCN1):c.314G>A (p.Arg105His)	CLCN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
359105	NM_000083.3(CLCN1):c.756G>A (p.Val252=)	CLCN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
359107	NM_000083.3(CLCN1):c.1205C>T (p.Ala402Val)	CLCN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
359108	NM_000083.3(CLCN1):c.1251+11G>T	CLCN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
359114	NM_000083.3(CLCN1):c.1842G>C (p.Lys614Asn)	CLCN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
359121	NM_000083.3(CLCN1):c.2230C>A (p.Pro744Thr)	CLCN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
359124	NM_000083.3(CLCN1):c.2545G>A (p.Ala849Thr)	CLCN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
359125	NM_000083.3(CLCN1):c.2550C>T (p.Tyr850=)	CLCN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 8 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SCN4A	Orphanet:681	Hypokalemic periodic paralysis
SCN4A	Orphanet:682	Hyperkalemic periodic paralysis
SCN4A	Orphanet:684	Paramyotonia congenita of Von Eulenburg
SCN4A	Orphanet:98913	Postsynaptic congenital myasthenic syndrome
SCN4A	Orphanet:99734	Myotonia fluctuans
SCN4A	Orphanet:99735	Myotonia permanens
SCN4A	Orphanet:99736	Acetazolamide-responsive myotonia
CLCN1	Orphanet:614	Thomsen and Becker disease

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SCN4A	HGNC:10591	ENSG00000007314	P35499	Sodium channel protein type 4 subunit alpha	clinvar
CLCN1	HGNC:2019	ENSG00000188037	P35523	Chloride channel protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SCN4A	Sodium channel protein type 4 subunit alpha	Pore-forming subunit of Nav1.4, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes.
CLCN1	Chloride channel protein 1	Voltage-gated chloride channel involved in skeletal muscle excitability.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Ion channel	1	55.8×	0.036
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SCN4A	Ion channel	yes		Na_channel_asu, Ion_trans_dom, Na_channel_a4su_mammal
CLCN1	Other/Unknown	no		ClC, Cl_channel-1, Cl-channel_core

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
hindlimb stylopod muscle	2
skeletal muscle tissue of rectus abdominis	2
gastrocnemius	1
triceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SCN4A	153	tissue_specific	yes	hindlimb stylopod muscle, gastrocnemius, skeletal muscle tissue of rectus abdominis
CLCN1	108	tissue_specific	marker	hindlimb stylopod muscle, triceps brachii, skeletal muscle tissue of rectus abdominis

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SCN4A	1,704
CLCN1	1,191

Intra-cohort edges

A	B	Sources
CLCN1	SCN4A	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CLCN1	P35523	9
SCN4A	P35499	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. Enrichment computed across 2 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Interaction between L1 and Ankyrins	1	184.2×	0.026	SCN4A
Phase 0 - rapid depolarisation	1	173.0×	0.026	SCN4A
Stimuli-sensing channels	1	68.0×	0.033	CLCN1
L1CAM interactions	1	60.1×	0.033	SCN4A
Cardiac conduction	1	54.4×	0.033	SCN4A
Muscle contraction	1	38.6×	0.039	SCN4A
Axon guidance	1	22.6×	0.052	SCN4A
Nervous system development	1	21.5×	0.052	SCN4A
Developmental Biology	1	7.2×	0.134	SCN4A

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
muscle contraction	2	208.1×	2e-04	SCN4A, CLCN1
regulation of skeletal muscle contraction by action potential	1	8426.0×	5e-04	SCN4A
neuronal action potential propagation	1	702.2×	0.004	CLCN1
cardiac muscle cell action potential involved in contraction	1	351.1×	0.006	SCN4A
chloride transport	1	227.7×	0.007	CLCN1
sodium ion transport	1	135.9×	0.010	SCN4A
chloride transmembrane transport	1	118.7×	0.010	CLCN1
sodium ion transmembrane transport	1	101.5×	0.010	SCN4A

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 1

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
SCN4A	CARBAMAZEPINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SCN4A	24	4
CLCN1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CARBAMAZEPINE	4	SCN4A
PHENYTOIN	4	SCN4A
LAMOTRIGINE	4	SCN4A
RILUZOLE	4	SCN4A
LIDOCAINE	4	SCN4A
IMIPRAMINE	4	SCN4A
SERTINDOLE	4	SCN4A
PIMOZIDE	4	SCN4A
NIFEDIPINE	4	SCN4A
DILTIAZEM	4	SCN4A
MIBEFRADIL	4	SCN4A
HALOPERIDOL	4	SCN4A
MEXILETINE	4	SCN4A
AMITRIPTYLINE	4	SCN4A
AMIODARONE	4	SCN4A
CHLORPROMAZINE	4	SCN4A
VIXOTRIGINE	3	SCN4A
ELECLAZINE	3	SCN4A
TETRODOTOXIN	3	SCN4A
TEDISAMIL	3	SCN4A
NITRENDIPINE	3	SCN4A
AJMALINE	3	SCN4A
PF-05089771	2	SCN4A
CIFENLINE	2	SCN4A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
SCN4A	95	Binding:69, Functional:18, ADMET:7, Toxicity:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

24 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
CARBAMAZEPINE	4	SCN4A
PHENYTOIN	4	SCN4A
LAMOTRIGINE	4	SCN4A
RILUZOLE	4	SCN4A
LIDOCAINE	4	SCN4A
IMIPRAMINE	4	SCN4A
SERTINDOLE	4	SCN4A
PIMOZIDE	4	SCN4A
NIFEDIPINE	4	SCN4A
DILTIAZEM	4	SCN4A
MIBEFRADIL	4	SCN4A
HALOPERIDOL	4	SCN4A
MEXILETINE	4	SCN4A
AMITRIPTYLINE	4	SCN4A
AMIODARONE	4	SCN4A
CHLORPROMAZINE	4	SCN4A
VIXOTRIGINE	3	SCN4A
ELECLAZINE	3	SCN4A
TETRODOTOXIN	3	SCN4A
TEDISAMIL	3	SCN4A
NITRENDIPINE	3	SCN4A
AJMALINE	3	SCN4A
PF-05089771	2	SCN4A
CIFENLINE	2	SCN4A

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SCN4A
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	CLCN1

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
CLCN1	0	SCN4A

Clinical trials & evidence

Clinical trials

Clinical trials: 0.