dilated cardiomyopathy 1I

Summary

dilated cardiomyopathy 1I (MONDO:0011482) is a disease caused by DES (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: DES (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 127

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	dilated cardiomyopathy 1I
Mondo ID	MONDO:0011482
MeSH	C565752
OMIM	604765
DOID	DOID:0110431
UMLS	C1858154
MedGen	387998
GARD	0015372
Is cancer (heuristic)	no

Also known as: cardiomyopathy, dilated, 1I · cardiomyopathy, dilated, type 1I · CMD1I · DES familial isolated dilated cardiomyopathy · dilated cardiomyopathy type 1I · familial isolated dilated cardiomyopathy caused by mutation in DES

Data availability: 127 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › qualitative or quantitative protein defects in neuromuscular diseases › neuromuscular disease caused by qualitative or quantitative defects of myofibrillar proteins › qualitative or quantitative defects of desmin › dilated cardiomyopathy 1I

Related subtypes (4): neurogenic scapuloperoneal syndrome, Kaeser type, myofibrillar myopathy 1, autosomal dominant limb-girdle muscular dystrophy type 1E (DES), rigid spine syndrome

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

127 retrieved; paginated sample, class counts are floors:

60 uncertain significance, 32 conflicting classifications of pathogenicity, 13 benign/likely benign, 9 likely pathogenic, 7 benign, 4 pathogenic/likely pathogenic, 1 pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
201722	NM_001927.4(DES):c.634C>T (p.Arg212Ter)	DES	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
643624	NM_001927.4(DES):c.226del (p.Thr76fs)	DES	Pathogenic	criteria provided, multiple submitters, no conflicts
66402	NM_001927.4(DES):c.1360C>T (p.Arg454Trp)	DES	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
66420	NM_001927.4(DES):c.735G>C (p.Glu245Asp)	DES	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
42735	NM_000256.3(MYBPC3):c.3697C>T (p.Gln1233Ter)	MYBPC3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1471108	NM_001927.4(DES):c.1130T>C (p.Leu377Pro)	DES	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3382173	NM_001927.4(DES):c.944dup (p.Gln316fs)	DES	Likely pathogenic	criteria provided, single submitter
3585680	NM_001927.4(DES):c.322del (p.Glu108fs)	DES	Likely pathogenic	criteria provided, single submitter
3767288	NM_001927.4(DES):c.376G>C (p.Val126Leu)	DES	Likely pathogenic	criteria provided, single submitter
3779565	NM_001927.4(DES):c.1265_1266del (p.Thr422fs)	DES	Likely pathogenic	criteria provided, single submitter
3779566	NM_001927.4(DES):c.1267_1268insTG (p.Tyr423fs)	DES	Likely pathogenic	criteria provided, single submitter
3779567	NM_001927.4(DES):c.1268_1269insT (p.Ser424fs)	DES	Likely pathogenic	criteria provided, single submitter
3896834	NM_001927.4(DES):c.1237del (p.Glu413fs)	DES	Likely pathogenic	criteria provided, single submitter
522692	NM_001927.4(DES):c.1151A>G (p.His384Arg)	DES	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071184	NM_001927.4(DES):c.885G>A (p.Trp295Ter)	DES	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
16820	NM_001927.4(DES):c.1009G>C (p.Ala337Pro)	DES	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
16824	NM_001927.4(DES):c.1353C>G (p.Ile451Met)	DES	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
178015	NM_001927.4(DES):c.635G>A (p.Arg212Gln)	DES	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
178016	NM_001927.4(DES):c.665G>A (p.Arg222His)	DES	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
193219	NM_001927.4(DES):c.216C>A (p.Ser72Arg)	DES	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
201708	NM_001927.4(DES):c.1205T>C (p.Ile402Thr)	DES	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
201709	NM_001927.4(DES):c.1243C>T (p.Arg415Trp)	DES	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
222542	NM_001927.4(DES):c.643G>A (p.Val215Met)	DES	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2573100	NM_001927.4(DES):c.736G>A (p.Glu246Lys)	DES	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
283467	NM_001927.4(DES):c.924C>T (p.Asn308=)	DES	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
290155	NM_001927.4(DES):c.-7C>G	DES	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
334451	NM_001927.4(DES):c.*198G>A	DES	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
411141	NM_001927.4(DES):c.679C>T (p.Arg227Cys)	DES	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
44244	NM_001927.4(DES):c.1048C>T (p.Arg350Trp)	DES	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
44254	NM_001927.4(DES):c.170C>T (p.Ser57Leu)	DES	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 15 · Orphanet: 5 · 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
DES	Definitive	Autosomal dominant	dilated cardiomyopathy 1I	15

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DES	Orphanet:154	Familial isolated dilated cardiomyopathy
DES	Orphanet:85146	Neurogenic scapuloperoneal syndrome, Kaeser type
DES	Orphanet:98909	Desminopathy
MYBPC3	Orphanet:154	Familial isolated dilated cardiomyopathy
MYBPC3	Orphanet:54260	Left ventricular noncompaction

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
DES	HGNC:2770	ENSG00000175084	P17661	Desmin	gencc,clinvar
MYBPC3	HGNC:7551	ENSG00000134571	Q14896	Myosin-binding protein C, cardiac-type	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DES	Desmin	Muscle-specific type III intermediate filament essential for proper muscular structure and function.
MYBPC3	Myosin-binding protein C, cardiac-type	Thick filament-associated protein located in the crossbridge region of vertebrate striated muscle a bands.

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
Antibody/Immunoglobulin	1	14.6×	0.135
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DES	Other/Unknown	no		Intermed_filament_DNA-bd, IF_conserved, IF_rod_dom
MYBPC3	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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
apex of heart	2
gastrocnemius	1
saphenous vein	1
cardiac atrium	1
right atrium auricular region	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DES	280	broad	marker	apex of heart, saphenous vein, gastrocnemius
MYBPC3	149	tissue_specific	marker	apex of heart, right atrium auricular region, cardiac atrium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DES	2,486
MYBPC3	1,800

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MYBPC3	Q14896	17

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DES	P17661	77.73

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
Striated Muscle Contraction	2	308.6×	2e-05	DES, MYBPC3
Muscle contraction	1	38.6×	0.026	MYBPC3

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
regulation of muscle filament sliding	1	4213.0×	0.003	MYBPC3
regulation of striated muscle contraction	1	1053.2×	0.004	MYBPC3
skeletal muscle organ development	1	1053.2×	0.004	DES
regulation of cardiac muscle cell contraction	1	561.7×	0.006	MYBPC3
nuclear envelope organization	1	495.6×	0.006	DES
ventricular cardiac muscle tissue morphogenesis	1	351.1×	0.007	MYBPC3
regulation of heart contraction	1	247.8×	0.007	DES
cardiac muscle contraction	1	200.6×	0.007	MYBPC3
sarcomere organization	1	191.5×	0.007	MYBPC3
heart morphogenesis	1	187.2×	0.007	MYBPC3
intermediate filament organization	1	120.4×	0.011	DES
muscle contraction	1	104.0×	0.011	DES
cytoskeleton organization	1	66.3×	0.016	DES
cell adhesion	1	18.7×	0.053	MYBPC3

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 2 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
DES	0	0
MYBPC3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

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	MYBPC3
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	DES

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)
DES	0	—
MYBPC3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.