Left ventricular noncompaction 2
diseaseOn this page
Also known as LVNC2
Summary
Left ventricular noncompaction 2 (MONDO:0012285) is a disease with 2 cohort genes.
At a glance
- Cohort genes: 2
- ClinVar variants: 4
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | left ventricular noncompaction 2 |
| Mondo ID | MONDO:0012285 |
| OMIM | 609470 |
| UMLS | C1836118 |
| MedGen | 322827 |
| GARD | 0015460 |
| Is cancer (heuristic) | no |
Also known as: left ventricular noncompaction 2 · LVNC2
Data availability: 4 ClinVar variants.
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 2
Related subtypes (12): dilated cardiomyopathy 1C, dilated cardiomyopathy 1D, left ventricular noncompaction 1, dilated cardiomyopathy 1Y, dilated cardiomyopathy 1R, dilated cardiomyopathy 1S, left ventricular noncompaction 7, left ventricular noncompaction 8, left ventricular noncompaction 10, 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
4 retrieved; paginated sample, class counts are floors:
1 uncertain significance, 1 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity, 1 likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 202537 | NM_001267550.2(TTN):c.45316_45320dup (p.Arg15108fs) | LOC126806427 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 265826 | NM_001267550.2(TTN):c.75727G>T (p.Glu25243Ter) | TTN-AS1 | Likely pathogenic | no assertion criteria provided |
| 203088 | NM_001267550.2(TTN):c.104978C>T (p.Thr34993Met) | TTN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1031089 | NM_001267550.2(TTN):c.42872C>T (p.Ala14291Val) | TTN | Uncertain significance | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 0 · Orphanet: 13 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| TTN | Orphanet:140922 | Titin-related limb-girdle muscular dystrophy R10 |
| TTN | Orphanet:154 | Familial isolated dilated cardiomyopathy |
| TTN | Orphanet:169186 | Autosomal recessive centronuclear myopathy |
| TTN | Orphanet:178464 | Hereditary myopathy with early respiratory failure |
| TTN | Orphanet:289377 | Early-onset myopathy with fatal cardiomyopathy |
| TTN | Orphanet:293888 | Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant |
| TTN | Orphanet:293899 | Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant |
| TTN | Orphanet:293910 | Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant |
| TTN | Orphanet:324604 | Classic multiminicore myopathy |
| TTN | Orphanet:334 | Hereditary atrial fibrillation |
| TTN | Orphanet:466921 | Childhood-onset progressive contractures-limb-girdle weakness-muscle dystrophy syndrome |
| TTN | Orphanet:609 | Tibial muscular dystrophy |
| TTN | Orphanet:707983 | Early-onset autosomal recessive TTN-related distal 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 |
|---|---|---|---|---|---|
| TTN | HGNC:12403 | ENSG00000155657 | Q8WZ42 | Titin | clinvar |
| TTN-AS1 | HGNC:44124 | ENSG00000237298 | TTN antisense RNA 1 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| TTN | Titin | Key component in the assembly and functioning of vertebrate striated muscles. |
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 |
|---|---|---|---|
| Kinase | 1 | 13.9× | 0.142 |
| Other/Unknown | 1 | 0.9× | 0.805 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| TTN | Kinase | yes | 2.7.11.1 | Prot_kinase_dom, Ig_sub2, Ig_sub |
| TTN-AS1 | Other/Unknown | no |
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 |
|---|---|
| biceps brachii | 1 |
| gluteal muscle | 1 |
| skeletal muscle tissue of biceps brachii | 1 |
| gastrocnemius | 1 |
| hindlimb stylopod muscle | 1 |
| right atrium auricular region | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| TTN | 223 | broad | marker | biceps brachii, gluteal muscle, skeletal muscle tissue of biceps brachii |
| TTN-AS1 | 174 | ubiquitous | marker | hindlimb stylopod muscle, gastrocnemius, right atrium auricular region |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| TTN | 4,237 |
| TTN-AS1 | 0 |
Structural data
PDB: 1 · AlphaFold-only: 0 · No structure: 1
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| TTN | Q8WZ42 | 64 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 2 evidence-associated genes (1 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 1 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 | 308.6× | 0.006 | TTN |
| Platelet degranulation | 1 | 87.8× | 0.011 | TTN |
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 |
|---|---|---|---|---|
| skeletal muscle myosin thick filament assembly | 1 | 5617.3× | 0.002 | TTN |
| sarcomerogenesis | 1 | 5617.3× | 0.002 | TTN |
| skeletal muscle thin filament assembly | 1 | 2808.7× | 0.002 | TTN |
| detection of muscle stretch | 1 | 2407.4× | 0.002 | TTN |
| cardiac muscle hypertrophy | 1 | 1685.2× | 0.002 | TTN |
| obsolete protein kinase A signaling | 1 | 1404.3× | 0.002 | TTN |
| cardiac muscle tissue morphogenesis | 1 | 1404.3× | 0.002 | TTN |
| cardiac myofibril assembly | 1 | 1296.3× | 0.002 | TTN |
| muscle filament sliding | 1 | 1053.2× | 0.002 | TTN |
| mitotic chromosome condensation | 1 | 991.3× | 0.002 | TTN |
| striated muscle contraction | 1 | 842.6× | 0.002 | TTN |
| cardiac muscle cell development | 1 | 624.1× | 0.003 | TTN |
| skeletal muscle contraction | 1 | 510.7× | 0.003 | TTN |
| cardiac muscle contraction | 1 | 401.2× | 0.003 | TTN |
| sarcomere organization | 1 | 383.0× | 0.003 | TTN |
| positive regulation of protein secretion | 1 | 343.9× | 0.003 | TTN |
| response to calcium ion | 1 | 318.0× | 0.004 | TTN |
| muscle contraction | 1 | 208.1× | 0.005 | TTN |
| positive regulation of gene expression | 1 | 38.7× | 0.026 | TTN |
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 |
|---|---|---|
| TTN | 0 | 0 |
| TTN-AS1 | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 1.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| TTN | 1 | Binding:1 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| TTN | 2.7.11.1 | non-specific serine/threonine protein kinase |
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 | 1 | TTN |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 1 | TTN-AS1 |
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) |
|---|---|---|
| TTN | 1 | — |
| TTN-AS1 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.