Left ventricular noncompaction 10

Summary

Left ventricular noncompaction 10 (MONDO:0014163) is a disease caused by MYBPC3 (GenCC Definitive), with 3 cohort genes.

At a glance

• Causal gene: MYBPC3 (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 353

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	left ventricular noncompaction 10
Mondo ID	MONDO:0014163
OMIM	615396
UMLS	C3715165
MedGen	811617
GARD	0015956
Is cancer (heuristic)	no

Also known as: left ventricular noncompaction 10 · left ventricular noncompaction caused by mutation in MYBPC3 · left ventricular noncompaction type 10 · LVNC10 · MYBPC3 left ventricular noncompaction

Data availability: 353 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › cardiomyopathy › intrinsic cardiomyopathy › left ventricular noncompaction › left ventricular noncompaction 10

Related subtypes (12): dilated cardiomyopathy 1C, dilated cardiomyopathy 1D, left ventricular noncompaction 1, left ventricular noncompaction 2, dilated cardiomyopathy 1Y, dilated cardiomyopathy 1R, dilated cardiomyopathy 1S, left ventricular noncompaction 7, left ventricular noncompaction 8, left ventricular noncompaction 9, left ventricular noncompaction 4, left ventricular noncompaction 5

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

353 retrieved; paginated sample, class counts are floors:

130 uncertain significance, 107 conflicting classifications of pathogenicity, 29 pathogenic/likely pathogenic, 28 pathogenic, 25 benign/likely benign, 13 likely pathogenic, 11 likely benign, 10 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
635764	arr[hg19]11p11.2(47339995x2,47343435_47375684x1,47387184x2)	MADD	Pathogenic	no assertion criteria provided
138326	NM_000256.3(MYBPC3):c.1224-19G>A	MYBPC3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
155808	NM_000256.3(MYBPC3):c.3190+5G>A	MYBPC3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
162506	NM_000256.3(MYBPC3):c.3642G>A (p.Trp1214Ter)	MYBPC3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
164091	NC_000011.10:g.47339718_47339719delinsC	MYBPC3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
164098	NM_000256.3(MYBPC3):c.1790G>A (p.Arg597Gln)	MYBPC3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
164109	NM_000256.3(MYBPC3):c.1591G>A (p.Gly531Arg)	MYBPC3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
164140	NC_000011.10:g.47347670del	MYBPC3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
177701	NM_000256.3(MYBPC3):c.3372C>A (p.Cys1124Ter)	MYBPC3	Pathogenic	criteria provided, multiple submitters, no conflicts
177837	NM_000256.3(MYBPC3):c.3190+1G>A	MYBPC3	Pathogenic	criteria provided, multiple submitters, no conflicts
181038	NM_000256.3(MYBPC3):c.484C>T (p.Gln162Ter)	MYBPC3	Pathogenic	criteria provided, multiple submitters, no conflicts
181064	NM_000256.3(MYBPC3):c.1201C>T (p.Gln401Ter)	MYBPC3	Pathogenic	criteria provided, multiple submitters, no conflicts
181080	NM_000256.3(MYBPC3):c.2511del (p.Ile837fs)	MYBPC3	Pathogenic	criteria provided, multiple submitters, no conflicts
181112	NM_000256.3(MYBPC3):c.884del (p.Phe295fs)	MYBPC3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
181156	NM_000256.3(MYBPC3):c.3467dup (p.Pro1157fs)	MYBPC3	Pathogenic	criteria provided, multiple submitters, no conflicts
188544	NM_000256.3(MYBPC3):c.1224-52G>A	MYBPC3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2075185	NM_000256.3(MYBPC3):c.2729del (p.Pro910fs)	MYBPC3	Pathogenic	criteria provided, multiple submitters, no conflicts
2132282	NM_000256.3(MYBPC3):c.2230_2233del (p.Glu744fs)	MYBPC3	Pathogenic	criteria provided, multiple submitters, no conflicts
222706	NM_000256.3(MYBPC3):c.1153_1168del (p.Val385fs)	MYBPC3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
222709	NM_000256.3(MYBPC3):c.3043dup (p.Ala1015fs)	MYBPC3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2582595	NM_000256.3(MYBPC3):c.226C>T (p.Gln76Ter)	MYBPC3	Pathogenic	criteria provided, multiple submitters, no conflicts
36604	NM_000256.3(MYBPC3):c.2308G>A (p.Asp770Asn)	MYBPC3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
36605	NM_000256.3(MYBPC3):c.2374T>C (p.Trp792Arg)	MYBPC3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
42525	NM_000256.3(MYBPC3):c.1351+2T>C	MYBPC3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
42540	NM_000256.3(MYBPC3):c.1504C>T (p.Arg502Trp)	MYBPC3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
42541	NM_000256.3(MYBPC3):c.1505G>A (p.Arg502Gln)	MYBPC3	Pathogenic	reviewed by expert panel
42550	NM_000256.3(MYBPC3):c.1591G>C (p.Gly531Arg)	MYBPC3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
42556	NM_000256.3(MYBPC3):c.1624+4A>T	MYBPC3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
42565	NM_000256.3(MYBPC3):c.177_187del (p.Glu60fs)	MYBPC3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
42585	NM_000256.3(MYBPC3):c.1928-2A>G	MYBPC3	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 13 · Orphanet: 6 · 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
MYBPC3	Definitive	Autosomal dominant	left ventricular noncompaction 10	13

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MYBPC3	Orphanet:154	Familial isolated dilated cardiomyopathy
MYBPC3	Orphanet:54260	Left ventricular noncompaction
ETFA	Orphanet:394529	Multiple acyl-CoA dehydrogenase deficiency, severe neonatal type
ETFA	Orphanet:394532	Multiple acyl-CoA dehydrogenase deficiency, mild type
MADD	Orphanet:528084	Non-specific syndromic intellectual disability
MADD	Orphanet:686495	MADD-related developmental delay-endocrine dysfunction-hypohemoglobinemia syndrome

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MYBPC3	HGNC:7551	ENSG00000134571	Q14896	Myosin-binding protein C, cardiac-type	gencc,clinvar
ETFA	HGNC:3481	ENSG00000140374	P13804	Electron transfer flavoprotein subunit alpha, mitochondrial	clinvar
MADD	HGNC:6766	ENSG00000110514	Q8WXG6	MAP kinase-activating death domain protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MYBPC3	Myosin-binding protein C, cardiac-type	Thick filament-associated protein located in the crossbridge region of vertebrate striated muscle a bands.
ETFA	Electron transfer flavoprotein subunit alpha, mitochondrial	Heterodimeric electron transfer flavoprotein that accepts electrons from several mitochondrial dehydrogenases, including acyl-CoA dehydrogenases, glutaryl-CoA and sarcosine dehydrogenase.
MADD	MAP kinase-activating death domain protein	Guanyl-nucleotide exchange factor that regulates small GTPases of the Rab family.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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	9.7×	0.199
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MYBPC3	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
ETFA	Other/Unknown	no		ETF_a/FixB, Rossmann-like_a/b/a_fold, ETF_a/b_N
MADD	Other/Unknown	no		cDENN_dom, dDENN_dom, uDENN_dom

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
apex of heart	1
cardiac atrium	1
right atrium auricular region	1
jejunal mucosa	1
oocyte	1
secondary oocyte	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MYBPC3	149	tissue_specific	marker	apex of heart, right atrium auricular region, cardiac atrium
ETFA	297	ubiquitous	marker	oocyte, secondary oocyte, jejunal mucosa
MADD	280	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ETFA	3,353
MYBPC3	1,800
MADD	1,021

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MYBPC3	Q14896	17
ETFA	P13804	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MADD	Q8WXG6	64.59

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 3 evidence-associated genes (3 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 3 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	102.9×	0.033	MYBPC3
Regulation of TNFR1 signaling	1	74.6×	0.033	MADD
RAB GEFs exchange GTP for GDP on RABs	1	41.4×	0.038	MADD
Respiratory electron transport	1	31.7×	0.038	ETFA
Muscle contraction	1	25.7×	0.038	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 3 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	2808.7×	0.005	MYBPC3
regulation of extrinsic apoptotic signaling pathway	1	1123.5×	0.005	MADD
amino acid catabolic process	1	936.2×	0.005	ETFA
regulation of Rab protein signal transduction	1	802.5×	0.005	MADD
regulation of extrinsic apoptotic signaling pathway via death domain receptors	1	802.5×	0.005	MADD
regulation of striated muscle contraction	1	702.2×	0.005	MYBPC3
fatty acid beta-oxidation using acyl-CoA dehydrogenase	1	468.1×	0.006	ETFA
regulation of cardiac muscle cell contraction	1	374.5×	0.006	MYBPC3
respiratory electron transport chain	1	280.9×	0.007	ETFA
execution phase of apoptosis	1	255.3×	0.007	MADD
ventricular cardiac muscle tissue morphogenesis	1	234.1×	0.007	MYBPC3
cardiac muscle contraction	1	133.8×	0.011	MYBPC3
sarcomere organization	1	127.7×	0.011	MYBPC3
heart morphogenesis	1	124.8×	0.011	MYBPC3
regulation of apoptotic process	1	27.8×	0.044	MADD
positive regulation of MAPK cascade	1	26.9×	0.044	MADD
regulation of cell cycle	1	24.9×	0.044	MADD
cell surface receptor signaling pathway	1	21.4×	0.049	MADD
cell adhesion	1	12.5×	0.078	MYBPC3

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MYBPC3	0	0
ETFA	0	0
MADD	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
ETFA	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	2	ETFA, MADD

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MYBPC3	0	—
ETFA	1	—
MADD	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.