Congenital myopathy 10b, mild variant

Summary

Congenital myopathy 10b, mild variant (MONDO:0859515) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 18

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital myopathy 10b, mild variant
Mondo ID	MONDO:0859515
OMIM	620249
DOID	DOID:0081345
UMLS	C3541476
MedGen	762102
GARD	0026731
Is cancer (heuristic)	no

Data availability: 18 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 › congenital myopathy 10b, mild variant

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, Batten-Turner congenital myopathy, TOR1AIP1-related myopathy, congenital myopathy 11, congenital myopathy 15, congenital myopathy 18, 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

18 retrieved; paginated sample, class counts are floors:

6 likely pathogenic, 5 pathogenic, 3 conflicting classifications of pathogenicity, 3 uncertain significance, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2443926	NM_001256545.2(MEGF10):c.2981-2A>G	MEGF10	Pathogenic	no assertion criteria provided
2443929	NM_001256545.2(MEGF10):c.2429G>A (p.Cys810Tyr)	MEGF10	Pathogenic	no assertion criteria provided
2443930	NM_001256545.2(MEGF10):c.352T>C (p.Cys118Arg)	MEGF10	Pathogenic	no assertion criteria provided
2443931	NM_001256545.2(MEGF10):c.1426+1G>T	MEGF10	Pathogenic	no assertion criteria provided
30965	NM_001256545.2(MEGF10):c.2320T>C (p.Cys774Arg)	MEGF10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
30966	NM_001256545.2(MEGF10):c.976T>C (p.Cys326Arg)	MEGF10	Pathogenic	criteria provided, single submitter
3384155	NM_001256545.2(MEGF10):c.[230G>A];[284del]		Likely pathogenic	criteria provided, single submitter
2443932	NM_001256545.2(MEGF10):c.2096G>C (p.Cys699Ser)	MEGF10	Likely pathogenic	criteria provided, single submitter
3767212	NM_001256545.2(MEGF10):c.1840+1G>A	MEGF10	Likely pathogenic	criteria provided, single submitter
3767213	NM_001256545.2(MEGF10):c.2233+758C>T	MEGF10	Likely pathogenic	criteria provided, single submitter
3779842	NM_001256545.2(MEGF10):c.1246del (p.Gln416fs)	MEGF10	Likely pathogenic	criteria provided, single submitter
4278160	NM_001256545.2(MEGF10):c.3132dup (p.Glu1045fs)	MEGF10	Likely pathogenic	criteria provided, single submitter
2197065	NM_001256545.2(MEGF10):c.2857-14T>A	MEGF10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3591679	NM_001256545.2(MEGF10):c.1041C>T (p.Gly347=)	MEGF10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
577106	NM_001256545.2(MEGF10):c.319C>T (p.Pro107Ser)	MEGF10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
30967	NM_001256545.2(MEGF10):c.211C>T (p.Arg71Trp)	MEGF10	Uncertain significance	criteria provided, single submitter
3896910	NM_001256545.2(MEGF10):c.1639G>A (p.Ala547Thr)	MEGF10	Uncertain significance	criteria provided, single submitter
851917	NM_001256545.2(MEGF10):c.2789A>G (p.Tyr930Cys)	MEGF10	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MEGF10	Orphanet:439212	Early-onset myopathy-areflexia-respiratory distress-dysphagia 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
MEGF10	HGNC:29634	ENSG00000145794	Q96KG7	Multiple epidermal growth factor-like domains protein 10	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MEGF10	Multiple epidermal growth factor-like domains protein 10	Membrane receptor involved in phagocytosis by macrophages and astrocytes of apoptotic cells.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MEGF10	Other/Unknown	no		EGF, LE_dom, EMI_domain

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
corpus callosum	1
lateral globus pallidus	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MEGF10	207	broad	marker	corpus callosum, ventricular zone, lateral globus pallidus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MEGF10	1,257

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MEGF10	Q96KG7	70.73

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
muscle cell proliferation	1	16852.0×	8e-04	MEGF10
regulation of skeletal muscle tissue development	1	8426.0×	8e-04	MEGF10
skeletal muscle satellite cell activation	1	5617.3×	8e-04	MEGF10
myoblast development	1	4213.0×	8e-04	MEGF10
skeletal muscle satellite cell proliferation	1	3370.4×	8e-04	MEGF10
recognition of apoptotic cell	1	2407.4×	8e-04	MEGF10
skeletal muscle satellite cell differentiation	1	2106.5×	8e-04	MEGF10
regulation of muscle cell differentiation	1	2106.5×	8e-04	MEGF10
engulfment of apoptotic cell	1	1872.4×	8e-04	MEGF10
myoblast migration	1	1872.4×	8e-04	MEGF10
homotypic cell-cell adhesion	1	1685.2×	8e-04	MEGF10
apoptotic process involved in development	1	1685.2×	8e-04	MEGF10
positive regulation of myoblast proliferation	1	1404.3×	9e-04	MEGF10
muscle cell development	1	936.2×	0.001	MEGF10
apoptotic cell clearance	1	887.0×	0.001	MEGF10
positive regulation of cell-cell adhesion	1	766.0×	0.001	MEGF10

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
MEGF10	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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	MEGF10

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)
MEGF10	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.