Hypertrophic cardiomyopathy 10

Summary

Hypertrophic cardiomyopathy 10 (MONDO:0012112) is a disease caused by MYL2 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: MYL2 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 452

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hypertrophic cardiomyopathy 10
Mondo ID	MONDO:0012112
MeSH	C563865
OMIM	608758
DOID	DOID:0110316
UMLS	C1834460
MedGen	331754
GARD	0024843
Is cancer (heuristic)	no

Also known as: cardiomyopathy, familial hypertrophic, 10 · cardiomyopathy, familial hypertrophic, type 10 · cardiomyopathy, hypertrophic, 10 · CMH10 · hypertrophic cardiomyopathy 10 · hypertrophic cardiomyopathy caused by mutation in MYL2 · hypertrophic cardiomyopathy type 10 · MYL2 hypertrophic cardiomyopathy

Data availability: 452 ClinVar variants · 2 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 10

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, long chain 3-hydroxyacyl-CoA dehydrogenase deficiency, cardiomyopathy-hypotonia-lactic acidosis syndrome, hypertrophic cardiomyopathy 11, hypertrophic cardiomyopathy 12, hypertrophic cardiomyopathy 13, 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

452 retrieved; paginated sample, class counts are floors:

228 uncertain significance, 145 likely benign, 47 conflicting classifications of pathogenicity, 16 benign/likely benign, 7 benign, 4 pathogenic/likely pathogenic, 3 likely pathogenic, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
14065	NM_000432.4(MYL2):c.64G>A (p.Glu22Lys)	LOC114827850	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
14068	NM_000432.4(MYL2):c.52T>C (p.Phe18Leu)	LOC114827850	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
14067	NM_000432.4(MYL2):c.173G>A (p.Arg58Gln)	MYL2	Pathogenic	criteria provided, multiple submitters, no conflicts
155818	NM_000432.4(MYL2):c.239C>A (p.Thr80Asn)	MYL2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
31769	NM_000432.4(MYL2):c.497A>T (p.Asp166Val)	MYL2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
417460	NC_000012.12:g.(?110910819)(110911175_?)del	MYL2	Pathogenic	criteria provided, single submitter
43479	NM_000432.4(MYL2):c.485G>A (p.Gly162Glu)	MYL2	Likely pathogenic	reviewed by expert panel
532778	NM_000432.4(MYL2):c.173G>T (p.Arg58Leu)	MYL2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
802892	NM_000432.4(MYL2):c.163G>C (p.Ala55Pro)	MYL2	Likely pathogenic	criteria provided, single submitter
1171989	NM_000432.4(MYL2):c.4-5C>G	LOC114827850	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
14064	NM_000432.4(MYL2):c.37G>A (p.Ala13Thr)	LOC114827850	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
177719	NM_000432.4(MYL2):c.45_46delinsT (p.Asn16fs)	LOC114827850	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
181423	NM_000432.4(MYL2):c.28G>A (p.Ala10Thr)	LOC114827850	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
181425	NM_000432.4(MYL2):c.53T>C (p.Phe18Ser)	LOC114827850	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
181430	NM_000432.4(MYL2):c.3+1G>T	LOC114827850	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3065627	NM_000432.4(MYL2):c.3+1G>A	LOC114827850	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
415511	NM_000432.4(MYL2):c.4-5C>T	LOC114827850	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
43481	NM_000432.4(MYL2):c.80A>G (p.Gln27Arg)	LOC114827850	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
444868	NM_000432.4(MYL2):c.3G>A (p.Met1Ile)	LOC114827850	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
802893	NM_000432.4(MYL2):c.3+2T>C	LOC114827850	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
927922	NM_000432.4(MYL2):c.4G>T (p.Ala2Ser)	LOC114827850	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
944169	NM_000432.4(MYL2):c.51_61del (p.Phe18fs)	LOC114827850	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1297593	NM_000432.4(MYL2):c.376C>T (p.Gln126Ter)	MYL2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
164478	NM_000432.4(MYL2):c.184A>T (p.Lys62Ter)	MYL2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
164481	NM_000432.4(MYL2):c.119G>A (p.Arg40Lys)	MYL2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
177958	NM_000432.4(MYL2):c.163G>T (p.Ala55Ser)	MYL2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
181420	NM_000432.4(MYL2):c.355G>A (p.Val119Ile)	MYL2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
181421	NM_000432.4(MYL2):c.488A>G (p.Glu163Gly)	MYL2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
181428	NM_000432.4(MYL2):c.103A>G (p.Ile35Val)	MYL2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
181433	NM_000432.4(MYL2):c.308T>G (p.Phe103Cys)	MYL2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
MYL2	Definitive	Autosomal dominant	hypertrophic cardiomyopathy 10	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MYL2	Orphanet:2020	Congenital fiber-type disproportion myopathy

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
MYL2	HGNC:7583	ENSG00000111245	P10916	Myosin regulatory light chain 2, ventricular/cardiac muscle isoform	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MYL2	Myosin regulatory light chain 2, ventricular/cardiac muscle isoform	Contractile protein that plays a role in heart development and function.

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)
MYL2	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
apex of heart	1
diaphragm	1
heart right ventricle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MYL2	179	tissue_specific	marker	heart right ventricle, diaphragm, apex of heart

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MYL2	3,119

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MYL2	P10916	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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×	0.006	MYL2
Muscle contraction	1	77.2×	0.013	MYL2

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
muscle cell fate specification	1	16852.0×	7e-04	MYL2
positive regulation of the force of heart contraction	1	3370.4×	0.002	MYL2
regulation of striated muscle contraction	1	2106.5×	0.002	MYL2
cardiac myofibril assembly	1	1296.3×	0.002	MYL2
regulation of the force of heart contraction	1	991.3×	0.002	MYL2
heart contraction	1	766.0×	0.002	MYL2
ventricular cardiac muscle tissue morphogenesis	1	702.2×	0.002	MYL2
cardiac muscle contraction	1	401.2×	0.003	MYL2
post-embryonic development	1	205.5×	0.006	MYL2
negative regulation of cell growth	1	144.0×	0.008	MYL2
heart development	1	78.8×	0.013	MYL2

Therapeutics

Drug target analysis

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

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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MYL2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	MYL2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MYL2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.