Myopathy, myosin storage, autosomal recessive

Summary

Myopathy, myosin storage, autosomal recessive (MONDO:0009708) is a disease caused by MYH7 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: MYH7 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 251

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	myopathy, myosin storage, autosomal recessive
Mondo ID	MONDO:0009708
MeSH	C564970
OMIM	255160
Orphanet	636970
DOID	DOID:0111268
UMLS	C1850709
MedGen	340603
GARD	0015207
Is cancer (heuristic)	no

Also known as: autosomal recessive myosin storage myopathy · MSMB · myopathy, myosin storage, autosomal recessive

Data availability: 251 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, myosin storage, autosomal recessive

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, 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 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

251 retrieved; paginated sample, class counts are floors:

136 uncertain significance, 35 conflicting classifications of pathogenicity, 17 likely benign, 15 benign, 15 pathogenic/likely pathogenic, 13 pathogenic, 11 benign/likely benign, 9 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
181261	NM_000257.4(MYH7):c.4664A>G (p.Glu1555Gly)	LOC126861897	Pathogenic	criteria provided, single submitter
36642	NM_000257.4(MYH7):c.5135G>A (p.Arg1712Gln)	LOC126861897	Pathogenic	reviewed by expert panel
164324	NM_000257.4(MYH7):c.2572C>T (p.Arg858Cys)	LOC126861898	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
164284	NM_000257.4(MYH7):c.4498C>T (p.Arg1500Trp)	MHRT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2671917	NM_000257.4(MYH7):c.4309G>C (p.Ala1437Pro)	MHRT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
132925	NM_000257.4(MYH7):c.1573G>A (p.Glu525Lys)	MYH7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
14087	NM_000257.4(MYH7):c.1208G>A (p.Arg403Gln)	MYH7	Pathogenic	reviewed by expert panel
14088	NM_000257.4(MYH7):c.746G>A (p.Arg249Gln)	MYH7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
14091	NM_000257.4(MYH7):c.1816G>A (p.Val606Met)	MYH7	Pathogenic	criteria provided, multiple submitters, no conflicts
14092	NM_000257.4(MYH7):c.2770G>A (p.Glu924Lys)	MYH7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
14095	NM_000257.4(MYH7):c.2167C>T (p.Arg723Cys)	MYH7	Pathogenic	reviewed by expert panel
14098	NM_000257.4(MYH7):c.2221G>C (p.Gly741Arg)	MYH7	Pathogenic	reviewed by expert panel
14102	NM_000257.4(MYH7):c.1207C>T (p.Arg403Trp)	MYH7	Pathogenic	reviewed by expert panel
14104	NM_000257.4(MYH7):c.2155C>T (p.Arg719Trp)	MYH7	Pathogenic	reviewed by expert panel
14124	NM_000257.4(MYH7):c.1491G>T (p.Glu497Asp)	MYH7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
14125	NM_000257.4(MYH7):c.2717A>G (p.Asp906Gly)	MYH7	Pathogenic	reviewed by expert panel
155814	NM_000257.4(MYH7):c.3158G>A (p.Arg1053Gln)	MYH7	Pathogenic	reviewed by expert panel
161328	NM_000257.4(MYH7):c.958G>A (p.Val320Met)	MYH7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
164312	NM_000257.4(MYH7):c.2788G>C (p.Glu930Gln)	MYH7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
177625	NM_000257.4(MYH7):c.1727A>G (p.His576Arg)	MYH7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
264068	NM_000257.4(MYH7):c.2081G>A (p.Arg694His)	MYH7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
42874	NM_000257.4(MYH7):c.1987C>T (p.Arg663Cys)	MYH7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
42875	NM_000257.4(MYH7):c.1988G>A (p.Arg663His)	MYH7	Pathogenic	reviewed by expert panel
42922	NM_000257.4(MYH7):c.2681A>G (p.Glu894Gly)	MYH7	Pathogenic	reviewed by expert panel
42992	NM_000257.4(MYH7):c.4130C>T (p.Thr1377Met)	MYH7	Pathogenic	reviewed by expert panel
43095	NM_000257.4(MYH7):c.611G>A (p.Arg204His)	MYH7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
43098	NM_000257.4(MYH7):c.709C>T (p.Arg237Trp)	MYH7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
43102	NM_000257.4(MYH7):c.732+1del	MYH7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
14118	NM_000257.4(MYH7):c.5134C>T (p.Arg1712Trp)	LOC126861897	Likely pathogenic	reviewed by expert panel
161326	NM_000257.4(MYH7):c.2608C>T (p.Arg870Cys)	LOC126861898	Likely pathogenic	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 20 · Orphanet: 7 · 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
MYH7	Definitive	Autosomal dominant	MYH7-related skeletal myopathy	20

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MYH7	Orphanet:154	Familial isolated dilated cardiomyopathy
MYH7	Orphanet:1880	Ebstein malformation of the tricuspid valve
MYH7	Orphanet:324604	Classic multiminicore myopathy
MYH7	Orphanet:54260	Left ventricular noncompaction
MYH7	Orphanet:59135	Laing distal myopathy
MYH7	Orphanet:636965	Autosomal dominant myosin storage myopathy
MYH7	Orphanet:636970	Autosomal recessive myosin storage myopathy

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MYH7	HGNC:7577	ENSG00000092054	P12883	Myosin-7	gencc,clinvar
MHRT	HGNC:51291			myosin heavy chain associated RNA transcript	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MYH7	Myosin-7	Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction.

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Scaffold/PPI	1	8.6×	0.225
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MYH7	Scaffold/PPI	no		IQ_motif_EF-hand-BS, Myosin_head_motor_dom-like, Myosin_tail
MHRT	Other/Unknown	no

Expression context

Cohort genes with no expression data: 1.

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	1

Top tissues across cohort

Tissue	Cohort genes
apex of heart	1
hindlimb stylopod muscle	1
skeletal muscle tissue of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MYH7	167	tissue_specific	marker	apex of heart, hindlimb stylopod muscle, skeletal muscle tissue of biceps brachii
MHRT

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MYH7	2,744
MHRT	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MYH7	P12883	43

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 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
regulation of slow-twitch skeletal muscle fiber contraction	1	8426.0×	0.001	MYH7
regulation of the force of skeletal muscle contraction	1	5617.3×	0.001	MYH7
transition between fast and slow fiber	1	2407.4×	0.002	MYH7
adult heart development	1	1203.7×	0.002	MYH7
cardiac muscle hypertrophy in response to stress	1	1053.2×	0.002	MYH7
muscle filament sliding	1	1053.2×	0.002	MYH7
regulation of the force of heart contraction	1	991.3×	0.002	MYH7
striated muscle contraction	1	842.6×	0.002	MYH7
ventricular cardiac muscle tissue morphogenesis	1	702.2×	0.002	MYH7
skeletal muscle contraction	1	510.7×	0.002	MYH7
regulation of heart rate	1	468.1×	0.002	MYH7
ATP metabolic process	1	468.1×	0.002	MYH7
cardiac muscle contraction	1	401.2×	0.003	MYH7
muscle contraction	1	208.1×	0.005	MYH7

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MYH7	0	0
MHRT	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	2	MYH7, MHRT

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MYH7	0	—
MHRT	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.