Myopathy, congenital, with tremor

Summary

Myopathy, congenital, with tremor (MONDO:0032797) is a disease caused by MYBPC1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: MYBPC1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 30

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	myopathy, congenital, with tremor
Mondo ID	MONDO:0032797
OMIM	618524
DOID	DOID:0081348
UMLS	C5231401
MedGen	1684886
GARD	0025748
Is cancer (heuristic)	no

Also known as: MYOTREM

Data availability: 30 ClinVar variants · 2 GenCC gene-disease records.

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 › myopathy, congenital, with tremor

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, 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, Batten-Turner congenital 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

30 retrieved; paginated sample, class counts are floors:

10 uncertain significance, 9 benign, 4 conflicting classifications of pathogenicity, 2 benign/likely benign, 2 pathogenic/likely pathogenic, 2 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
225889	NM_002465.4(MYBPC1):c.742G>A (p.Glu248Lys)	MYBPC1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
522829	NM_002465.4(MYBPC1):c.776T>C (p.Leu259Pro)	MYBPC1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
635215	NM_002465.4(MYBPC1):c.788T>G (p.Leu263Arg)	MYBPC1	Pathogenic	criteria provided, multiple submitters, no conflicts
689419	NM_002465.4(MYBPC1):c.739T>C (p.Tyr247His)	MYBPC1	Pathogenic	no assertion criteria provided
4082076	NM_002465.4(MYBPC1):c.795_803dup (p.Arg268_Met269insLeuLysArg)	MYBPC1	Likely pathogenic	criteria provided, single submitter
306730	NM_002465.4(MYBPC1):c.1250G>A (p.Arg417Lys)	LOC105369937	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
39766	NM_002465.4(MYBPC1):c.952C>T (p.Arg318Ter)	MYBPC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
435910	NM_002465.4(MYBPC1):c.2510T>G (p.Val837Gly)	MYBPC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
882507	NM_002465.4(MYBPC1):c.1399C>G (p.Gln467Glu)	MYBPC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1211435	NM_002465.4(MYBPC1):c.437G>A (p.Arg146Gln)	MYBPC1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2433858	NM_002465.4(MYBPC1):c.787C>T (p.Leu263Phe)	MYBPC1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3242127	NM_002465.4(MYBPC1):c.608+5C>T	MYBPC1	Uncertain significance	criteria provided, single submitter
3891767	NM_002465.4(MYBPC1):c.1760G>C (p.Gly587Ala)	MYBPC1	Uncertain significance	criteria provided, single submitter
3891768	NM_002465.4(MYBPC1):c.2573G>A (p.Arg858His)	MYBPC1	Uncertain significance	criteria provided, single submitter
3891769	NM_002465.4(MYBPC1):c.271G>A (p.Gly91Arg)	MYBPC1	Uncertain significance	criteria provided, single submitter
3894562	NM_002465.4(MYBPC1):c.644T>C (p.Phe215Ser)	MYBPC1	Uncertain significance	criteria provided, single submitter
3896924	NM_002465.4(MYBPC1):c.532T>C (p.Cys178Arg)	MYBPC1	Uncertain significance	criteria provided, single submitter
3905598	NM_002465.4(MYBPC1):c.781G>A (p.Gly261Ser)	MYBPC1	Uncertain significance	criteria provided, multiple submitters, no conflicts
4813683	NM_002465.4(MYBPC1):c.3224G>C (p.Cys1075Ser)	MYBPC1	Uncertain significance	criteria provided, single submitter
1228159	NM_002465.4(MYBPC1):c.2222-38T>C	MYBPC1	Benign	criteria provided, multiple submitters, no conflicts
1276920	NM_002465.4(MYBPC1):c.3492+39C>T	MYBPC1	Benign	criteria provided, multiple submitters, no conflicts
1277918	NM_002465.4(MYBPC1):c.1633+33T>C	MYBPC1	Benign	criteria provided, multiple submitters, no conflicts
129642	NM_002465.4(MYBPC1):c.1518C>G (p.His506Gln)	MYBPC1	Benign	criteria provided, multiple submitters, no conflicts
129644	NM_002465.4(MYBPC1):c.2544T>C (p.Ile848=)	MYBPC1	Benign	criteria provided, multiple submitters, no conflicts
129645	NM_002465.4(MYBPC1):c.2817A>G (p.Pro939=)	MYBPC1	Benign	criteria provided, multiple submitters, no conflicts
129647	NM_002465.4(MYBPC1):c.774C>T (p.Asp258=)	MYBPC1	Benign	criteria provided, multiple submitters, no conflicts
211545	NM_002465.4(MYBPC1):c.594T>C (p.Ser198=)	MYBPC1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
258658	NM_002465.4(MYBPC1):c.1634-18del	MYBPC1	Benign	criteria provided, multiple submitters, no conflicts
306725	NM_002465.4(MYBPC1):c.608+14A>G	MYBPC1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
306752	NM_002465.4(MYBPC1):c.*78G>A	MYBPC1	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
MYBPC1	Strong	Autosomal recessive	lethal congenital contracture syndrome 4	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MYBPC1	Orphanet:1146	Distal arthrogryposis type 1
MYBPC1	Orphanet:137783	Lethal congenital contracture syndrome type 3
MYBPC1	Orphanet:498693	MYBPC1-related autosomal recessive non-lethal arthrogryposis multiplex congenita syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MYBPC1	HGNC:7549	ENSG00000196091	Q00872	Myosin-binding protein C, slow-type	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MYBPC1	Myosin-binding protein C, slow-type	Thick filament-associated protein located in the crossbridge region of vertebrate striated muscle a bands.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MYBPC1	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom

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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
biceps brachii	1
skeletal muscle tissue of biceps brachii	1
skeletal muscle tissue of rectus abdominis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MYBPC1	225	broad	marker	biceps brachii, skeletal muscle tissue of rectus abdominis, skeletal muscle tissue of biceps brachii

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MYBPC1	1,816

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MYBPC1	Q00872	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Striated Muscle Contraction	1	308.6×	0.006	MYBPC1
Muscle contraction	1	77.2×	0.013	MYBPC1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
sarcomere organization	1	383.0×	0.005	MYBPC1
cell adhesion	1	37.5×	0.027	MYBPC1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MYBPC1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	MYBPC1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
MYBPC1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.