Hypertrophic cardiomyopathy 13

Summary

Hypertrophic cardiomyopathy 13 (MONDO:0013195) is a disease caused by TNNC1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: TNNC1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 320

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hypertrophic cardiomyopathy 13
Mondo ID	MONDO:0013195
MeSH	C567686
OMIM	613243
DOID	DOID:0110319
UMLS	C2750472
MedGen	442487
GARD	0024906
Is cancer (heuristic)	no

Also known as: cardiomyopathy, familial hypertrophic, 13 · cardiomyopathy, familial hypertrophic, type 13 · cardiomyopathy, hypertrophic, 13 · CMH13 · hypertrophic cardiomyopathy caused by mutation in TNNC1 · hypertrophic cardiomyopathy type 13 · TNNC1 hypertrophic cardiomyopathy

Data availability: 320 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 › hypertrophic cardiomyopathy › familial hypertrophic cardiomyopathy › hypertrophic cardiomyopathy 13

Related subtypes (39): hypertrophic cardiomyopathy 2, hypertrophic cardiomyopathy 3, hypertrophic cardiomyopathy 4, Beckwith-Wiedemann syndrome, myotonic dystrophy type 1, hypertrophic cardiomyopathy 1, very long chain acyl-CoA dehydrogenase deficiency, multiple acyl-CoA dehydrogenase deficiency, 46,XY complete gonadal dysgenesis, hypertrophic cardiomyopathy 6, dilated cardiomyopathy 1C, hypertrophic cardiomyopathy 25, hypertrophic cardiomyopathy 8, hypertrophic cardiomyopathy 10, long chain 3-hydroxyacyl-CoA dehydrogenase deficiency, cardiomyopathy-hypotonia-lactic acidosis syndrome, hypertrophic cardiomyopathy 11, hypertrophic cardiomyopathy 12, hypertrophic cardiomyopathy 14, hypertrophic cardiomyopathy 15, hypertrophic cardiomyopathy 7, hypertrophic cardiomyopathy 9, hypertrophic cardiomyopathy 16, hypertrophic cardiomyopathy 17, hypertrophic cardiomyopathy 18, hypertrophic cardiomyopathy 19, hypertrophic cardiomyopathy 20, hypertrophic cardiomyopathy 21, dilated cardiomyopathy 1KK, hypertrophic cardiomyopathy 26, Noonan syndrome and Noonan-related syndrome, long chain acyl-CoA dehydrogenase deficiency, cardiomyopathy, familial hypertrophic, 28, cardiomyopathy, familial hypertrophic 27, cardiomyopathy, familial hypertrophic, 23, with or without ventricular noncompaction, cardiomyopathy, familial restrictive, 5, cardiomyopathy, familial hypertrophic, 29, with polyglucosan bodies, cardiomyopathy, familial hypertrophic, 30, atrial, cardiomyopathy, familial hypertrophic, 31

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

320 retrieved; paginated sample, class counts are floors:

167 uncertain significance, 120 likely benign, 21 conflicting classifications of pathogenicity, 7 benign/likely benign, 2 benign, 1 likely pathogenic, 1 pathogenic/likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
12443	NM_003280.3(TNNC1):c.23C>T (p.Ala8Val)	TNNC1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
39832	NM_003280.3(TNNC1):c.91G>T (p.Ala31Ser)	TNNC1	Pathogenic	criteria provided, single submitter
1066522	NM_003280.3(TNNC1):c.168G>C (p.Glu56Asp)	TNNC1	Likely pathogenic	criteria provided, single submitter
1397389	NM_003280.3(TNNC1):c.14A>G (p.Tyr5Cys)	TNNC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
165498	NM_003280.3(TNNC1):c.56-8G>A	TNNC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
179034	NM_003280.3(TNNC1):c.108C>A (p.Ile36=)	TNNC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
179947	NM_003280.3(TNNC1):c.203-10C>G	TNNC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
181563	NM_003280.3(TNNC1):c.262G>A (p.Asp88Asn)	TNNC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
181567	NM_003280.3(TNNC1):c.430A>G (p.Asn144Asp)	TNNC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
181572	NM_003280.3(TNNC1):c.155C>G (p.Pro52Arg)	TNNC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
346128	NM_003280.3(TNNC1):c.*127C>T	TNNC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
346131	NM_003280.3(TNNC1):c.81C>T (p.Phe27=)	TNNC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
346132	NM_003280.3(TNNC1):c.55+9C>A	TNNC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
382597	NM_003280.3(TNNC1):c.24+6G>A	TNNC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
415848	NM_003280.3(TNNC1):c.454+7G>A	TNNC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
44677	NM_003280.3(TNNC1):c.210C>T (p.Gly70=)	TNNC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
44679	NM_003280.3(TNNC1):c.387G>C (p.Thr129=)	TNNC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
44683	NM_003280.3(TNNC1):c.445G>A (p.Asp149Asn)	TNNC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
508670	NM_003280.3(TNNC1):c.454+6C>T	TNNC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
537986	NM_003280.3(TNNC1):c.195C>T (p.Asp65=)	TNNC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
626721	NM_003280.3(TNNC1):c.216G>A (p.Val72=)	TNNC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
700167	NM_003280.3(TNNC1):c.444C>T (p.Ile148=)	TNNC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
702219	NM_003280.3(TNNC1):c.213G>C (p.Thr71=)	TNNC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
948109	NM_003280.3(TNNC1):c.455-6C>G	TNNC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1002556	NM_003280.3(TNNC1):c.208G>A (p.Gly70Ser)	TNNC1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1014893	NM_003280.3(TNNC1):c.186T>G (p.Asp62Glu)	TNNC1	Uncertain significance	criteria provided, single submitter
1014965	NM_003280.3(TNNC1):c.221T>G (p.Phe74Cys)	TNNC1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1015264	NM_003280.3(TNNC1):c.125G>A (p.Gly42Asp)	TNNC1	Uncertain significance	criteria provided, single submitter
1016295	NM_003280.3(TNNC1):c.180G>A (p.Met60Ile)	TNNC1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1024458	NM_003280.3(TNNC1):c.196G>A (p.Glu66Lys)	TNNC1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 1 · 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
TNNC1	Definitive	Autosomal dominant	hypertrophic cardiomyopathy	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TNNC1	Orphanet:154	Familial isolated dilated cardiomyopathy

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TNNC1	HGNC:11943	ENSG00000114854	P63316	Troponin C, slow skeletal and cardiac muscles	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TNNC1	Troponin C, slow skeletal and cardiac muscles	Troponin is the central regulatory protein of striated muscle contraction.

Protein-family classification

Druggable: 0 · Difficult: 0 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TNNC1	Other/Unknown	no		EF_hand_dom, EF-hand-dom_pair, EF_Hand_1_Ca_BS

Expression context

Cohort genes with no expression data: 0.

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	0

Top tissues across cohort

Tissue	Cohort genes
gluteal muscle	1
heart right ventricle	1
triceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TNNC1	207	broad	marker	triceps brachii, gluteal muscle, heart right ventricle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TNNC1	73

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TNNC1	P63316	61

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 1 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×	0.003	TNNC1

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 muscle filament sliding speed	1	16852.0×	6e-04	TNNC1
diaphragm contraction	1	4213.0×	0.001	TNNC1
transition between fast and slow fiber	1	2407.4×	0.001	TNNC1
regulation of muscle contraction	1	1685.2×	0.001	TNNC1
cardiac muscle cell contraction	1	1685.2×	0.001	TNNC1
response to metal ion	1	1532.0×	0.001	TNNC1
muscle filament sliding	1	1053.2×	0.001	TNNC1
ventricular cardiac muscle tissue morphogenesis	1	702.2×	0.002	TNNC1
skeletal muscle contraction	1	510.7×	0.002	TNNC1
cardiac muscle contraction	1	401.2×	0.002	TNNC1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
TNNC1	FINGOLIMOD

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TNNC1	2	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FINGOLIMOD	4	TNNC1
LEVOSIMENDAN	3	TNNC1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TNNC1	8	Binding:8

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

2 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.

Compound	Max phase	Cohort target (bioactivity)
FINGOLIMOD	4	TNNC1
LEVOSIMENDAN	3	TNNC1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	TNNC1
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.