congenital myopathy 7A, myosin storage, autosomal dominant

Summary

congenital myopathy 7A, myosin storage, autosomal dominant (MONDO:0008409) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 392

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital myopathy 7A, myosin storage, autosomal dominant
Mondo ID	MONDO:0008409
MeSH	C564253
OMIM	181430, 608358
Orphanet	636965, 437572
DOID	DOID:0111269
UMLS	C1842160
MedGen	374868
GARD	0015429
Is cancer (heuristic)	no

Also known as: autosomal dominant myosin storage myopathy · MSMA · MYH7-related late-onset scapuloperoneal muscular dystrophy · MYH7-related late-onset scapuloperoneal syndrome · MYH7-related late-onset SPMD · MYH7-related scapuloperoneal myopathy · myopathy with lysis of type 1 myofibrils · myopathy, hyaline body, autosomal dominant · myopathy, myosin storage, autosomal dominant · scapuloperoneal muscular dystrophy · scapuloperoneal myopathy, MYH7-related · scapuloperoneal syndrome, myopathic type · SPMD · SPMM

Data availability: 392 ClinVar variants · 1 ClinGen variant curation · 1 GenCC gene-disease record.

Disease family

Classification path: human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › skeletal muscle disorder › myopathy › muscular dystrophy › progressive muscular dystrophy › Emery-Dreifuss muscular dystrophy › scapuloperoneal myopathy › congenital myopathy 7A, myosin storage, autosomal dominant

Related subtypes (1): X-linked scapuloperoneal muscular dystrophy

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

392 retrieved; paginated sample, class counts are floors:

165 uncertain significance, 109 conflicting classifications of pathogenicity, 34 benign, 20 likely benign, 17 pathogenic/likely pathogenic, 17 likely pathogenic, 15 benign/likely benign, 15 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
143214	NM_000257.4(MYH7):c.4937T>C (p.Leu1646Pro)	LOC126861897	Pathogenic	criteria provided, multiple submitters, no conflicts
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
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
14117	NM_000257.4(MYH7):c.5702A>T (p.His1901Leu)	MYH7	Pathogenic	no assertion criteria provided
14123	NM_000257.4(MYH7):c.5378T>C (p.Leu1793Pro)	MYH7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
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
177897	NM_000257.4(MYH7):c.1324C>T (p.Arg442Cys)	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
42820	NM_000257.4(MYH7):c.1063G>A (p.Ala355Thr)	MYH7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
42838	NM_000257.4(MYH7):c.1358G>A (p.Arg453His)	MYH7	Pathogenic	reviewed by expert panel
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

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.