Hypertrophic cardiomyopathy 14

Summary

Hypertrophic cardiomyopathy 14 (MONDO:0013197) is a disease caused by MYH6 (GenCC Strong), with 6 cohort genes.

At a glance

• Causal gene: MYH6 (GenCC Strong)
• Cohort genes: 6
• ClinVar variants: 2,032

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hypertrophic cardiomyopathy 14
Mondo ID	MONDO:0013197
MeSH	C567684
OMIM	613251
DOID	DOID:0110320
UMLS	C2750467
MedGen	442484
GARD	0024907
Is cancer (heuristic)	no

Also known as: cardiomyopathy, familial hypertrophic, 14 · cardiomyopathy, familial hypertrophic, type 14 · cardiomyopathy, hypertrophic, 14 · CMH14 · hypertrophic cardiomyopathy caused by mutation in MYH6 · hypertrophic cardiomyopathy type 14 · MYH6 hypertrophic cardiomyopathy

Data availability: 2,032 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 14

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 13, 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

600 retrieved; paginated sample, class counts are floors:

330 uncertain significance, 214 likely benign, 34 conflicting classifications of pathogenicity, 19 benign/likely benign, 3 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1447754	NM_002471.4(MYH6):c.616AAG[1] (p.Lys207del)	LOC114827851	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
164256	NM_002471.4(MYH6):c.245C>T (p.Pro82Leu)	LOC114827851	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1355033	NM_002471.4(MYH6):c.4985C>T (p.Ala1662Val)	LOC126861896	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1421998	NM_002471.4(MYH6):c.5020G>A (p.Ala1674Thr)	LOC126861896	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
178065	NM_002471.4(MYH6):c.4905C>T (p.Asn1635=)	LOC126861896	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1032059	NM_002471.4(MYH6):c.1411-12T>C	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1079894	NM_002471.4(MYH6):c.3981G>A (p.Ala1327=)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1123081	NM_002471.4(MYH6):c.3099G>A (p.Val1033=)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1156267	NM_002471.4(MYH6):c.852C>T (p.Tyr284=)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1284635	NM_002471.4(MYH6):c.2717G>A (p.Arg906His)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1376992	NM_002471.4(MYH6):c.2064C>A (p.Asn688Lys)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
14149	NM_002471.4(MYH6):c.3195G>C (p.Gln1065His)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
14151	NM_002471.4(MYH6):c.3010G>T (p.Ala1004Ser)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1432256	NM_002471.4(MYH6):c.409G>A (p.Glu137Lys)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
155811	NM_002471.4(MYH6):c.1763A>C (p.Asp588Ala)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
164227	NM_002471.4(MYH6):c.3979-8_3979-7delinsGC	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
164230	NM_002471.4(MYH6):c.3508G>A (p.Glu1170Lys)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
164242	NM_002471.4(MYH6):c.2071G>A (p.Val691Ile)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
164244	NM_002471.4(MYH6):c.1582-7C>T	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1712631	NM_002471.4(MYH6):c.1894G>A (p.Asp632Asn)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1749671	NM_002471.4(MYH6):c.5792C>T (p.Ala1931Val)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
177985	NM_002471.4(MYH6):c.831G>T (p.Gln277His)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
178066	NM_002471.4(MYH6):c.4595G>T (p.Arg1532Leu)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
178067	NM_002471.4(MYH6):c.4360-7C>G	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
178072	NM_002471.4(MYH6):c.1702C>T (p.Arg568Cys)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
178075	NM_002471.4(MYH6):c.1132G>A (p.Gly378Ser)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1781975	NM_002471.4(MYH6):c.1885G>A (p.Asp629Asn)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
179023	NM_002471.4(MYH6):c.3220G>A (p.Asp1074Asn)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
179024	NM_002471.4(MYH6):c.2464G>A (p.Ala822Thr)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1794723	NM_002471.4(MYH6):c.2686-5C>T	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 9 · 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
MYH6	Strong	Autosomal dominant	hypertrophic cardiomyopathy 14	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MYH6	Orphanet:154	Familial isolated dilated cardiomyopathy
MYH6	Orphanet:166282	Hereditary sick sinus syndrome
MYH6	Orphanet:99103	Atrial septal defect, ostium secundum type
LDB3	Orphanet:154	Familial isolated dilated cardiomyopathy
LDB3	Orphanet:293888	Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant
LDB3	Orphanet:293899	Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant
LDB3	Orphanet:293910	Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant
LDB3	Orphanet:54260	Left ventricular noncompaction
LDB3	Orphanet:98912	Late-onset distal myopathy, Markesbery-Griggs type

Cohort genes → proteins

6 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MYH6	HGNC:7576	ENSG00000197616	P13533	Myosin-6	gencc,clinvar
LDB3	HGNC:15710	ENSG00000122367	O75112	LIM domain-binding protein 3	clinvar
MIR208A	HGNC:31585	ENSG00000199157		microRNA 208a	clinvar
MIR208B	HGNC:33669	ENSG00000215991		microRNA 208b	clinvar
FRZB	HGNC:3959	ENSG00000162998	Q92765	Secreted frizzled-related protein 3	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)
MYH6	Myosin-6	Muscle contraction.
LDB3	LIM domain-binding protein 3	May function as an adapter in striated muscle to couple protein kinase C-mediated signaling via its LIM domains to the cytoskeleton.
FRZB	Secreted frizzled-related protein 3	Soluble frizzled-related proteins (sFRPS) function as modulators of Wnt signaling through direct interaction with Wnts.

Protein-family classification

Druggable: 0 · Difficult: 2 · Unknown: 4 · 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	2.9×	0.539
Transcription factor	1	1.4×	0.539
Other/Unknown	4	1.2×	0.539

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MYH6	Scaffold/PPI	no		Myosin_head_motor_dom-like, Myosin_tail, SH3_Myosin
LDB3	Transcription factor	no		PDZ, Znf_LIM, Zasp-like_motif
MIR208A	Other/Unknown	no
MIR208B	Other/Unknown	no
FRZB	Other/Unknown	no		Netrin_domain, TIMP-like_OB-fold, Frizzled/SFRP
MHRT	Other/Unknown	no

Expression context

Cohort genes with no expression data: 1.

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)	5
unknown	1

Top tissues across cohort

Tissue	Cohort genes
apex of heart	2
cardiac atrium	1
cardiac muscle of right atrium	1
vena cava	1
hindlimb stylopod muscle	1
skeletal muscle tissue of biceps brachii	1
heart	1
right atrium auricular region	1
skeletal muscle tissue	1
body of pancreas	1
pancreas	1
pigmented layer of retina	1
retina	1
right coronary artery	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MYH6	154	tissue_specific	yes	cardiac muscle of right atrium, cardiac atrium, vena cava
LDB3	247	broad	marker	skeletal muscle tissue of biceps brachii, hindlimb stylopod muscle, apex of heart
MIR208A	37		yes	right atrium auricular region, skeletal muscle tissue, heart
MIR208B	55		yes	body of pancreas, apex of heart, pancreas
FRZB	269	broad	marker	pigmented layer of retina, retina, right coronary artery
MHRT

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MYH6	3,119
FRZB	1,865
LDB3	1,275
MIR208A	0
MIR208B	0
MHRT	0

Structural data

PDB: 1 · AlphaFold-only: 2 · No structure: 3

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LDB3	O75112	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FRZB	Q92765	81.00
MYH6	P13533	74.91

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 6 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	MYH6
Muscle contraction	1	77.2×	0.013	MYH6

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
sarcomere organization	2	255.3×	8e-04	MYH6, LDB3
visceral muscle development	1	5617.3×	0.002	MYH6
negative regulation of hepatocyte differentiation	1	5617.3×	0.002	FRZB
negative regulation of cell development	1	2808.7×	0.002	FRZB
convergent extension involved in organogenesis	1	2808.7×	0.002	FRZB
regulation of heart growth	1	2808.7×	0.002	MYH6
atrial cardiac muscle tissue morphogenesis	1	802.5×	0.007	MYH6
negative regulation of cartilage development	1	702.2×	0.007	FRZB
epithelial cell development	1	510.7×	0.007	FRZB
neural crest cell differentiation	1	510.7×	0.007	FRZB
muscle structure development	1	468.1×	0.007	LDB3
adult heart development	1	401.2×	0.007	MYH6
hepatocyte differentiation	1	401.2×	0.007	FRZB
myofibril assembly	1	374.5×	0.007	MYH6
somite development	1	374.5×	0.007	FRZB
cardiac muscle hypertrophy in response to stress	1	351.1×	0.007	MYH6
muscle filament sliding	1	351.1×	0.007	MYH6
regulation of the force of heart contraction	1	330.4×	0.007	MYH6
striated muscle contraction	1	280.9×	0.007	MYH6
ventricular cardiac muscle tissue morphogenesis	1	234.1×	0.009	MYH6
cardiac muscle cell development	1	208.1×	0.009	MYH6
non-canonical Wnt signaling pathway	1	193.7×	0.009	FRZB
cochlea morphogenesis	1	193.7×	0.009	FRZB
regulation of heart contraction	1	165.2×	0.010	MYH6
regulation of heart rate	1	156.0×	0.010	MYH6
ATP metabolic process	1	156.0×	0.010	MYH6
cardiac muscle contraction	1	133.8×	0.011	MYH6
negative regulation of Wnt signaling pathway	1	114.6×	0.012	FRZB
positive regulation of fat cell differentiation	1	100.3×	0.014	FRZB
regulation of blood pressure	1	73.9×	0.018	MYH6

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 6

Druggability breadth: 1 of 6 evidence-associated genes (17%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MYH6	0	0
LDB3	0	0
MIR208A	0	0
MIR208B	0	0
FRZB	0	0
MHRT	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; 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	6	MYH6, LDB3, MIR208A, MIR208B, FRZB, MHRT

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MYH6	0	—
LDB3	0	—
MIR208A	0	—
MIR208B	0	—
FRZB	0	—
MHRT	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.