Dilated Cardiomyopathy 1S

Genetic MONDO:0013262 Pathograph 5 Show in embeddings browser Dilated Cardiomyopathy Genetic Disorder

Dilated cardiomyopathy 1S (CMD1S) is the MYH7-related form of familial isolated dilated cardiomyopathy. MYH7 encodes the beta-cardiac myosin heavy chain, the force-generating motor of the thick filament - the same protein whose variants cause hypertrophic cardiomyopathy 1 (CMH1). CMD1S is therefore the cleanest illustration in the knowledge base of a principle that the founding study of sarcomeric dilated cardiomyopathy set out explicitly: distinct mutations in one sarcomere protein cause either dilated or hypertrophic disease, so the mutant motor must trigger two different remodelling programmes. Where hypertrophic MYH7 alleles act by a gain of contractile function, the dilated alleles diminish contractile function. Kamisago and colleagues established the entity in 2000 by mapping a dilated cardiomyopathy locus to 14q11.2-13, where MYH7 is encoded, and identifying dominant missense alleles (Ser532Pro, Phe764Leu) that produced early-onset ventricular dilatation with diminished contractile function and no antecedent hypertrophy. ClinGen classifies the MYH7-dilated cardiomyopathy relationship as Definitive with autosomal dominant inheritance.

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1
Inheritance
4
Pathophys.
2
Phenotypes
5
Pathograph
1
Genes
2
Medical Actions
1
References
🏷

Classifications

Harrison's Part
CARDIOVASCULAR GENETICS ENVIRONMENT DISEASE
👪

Inheritance

1
Autosomal dominant HP:0000006
CMD1S is inherited as an autosomal dominant trait; a single MYH7 missense allele causes disease. Onset is characteristically early - the founding kindreds averaged 24 years at diagnosis - which is one of the features distinguishing sarcomeric from non-sarcomeric familial dilated cardiomyopathy.
Autosomal dominant inheritance Penetrance: INCOMPLETE
Show evidence (2 references)
CGGV:assertion_4ec27d4f-70ea-4c6a-ad67-d6260ecadcde-2025-05-30T160000.000Z SUPPORT Other
"MYH7 | HGNC:7577 | dilated cardiomyopathy | MONDO:0005021 | AD | Definitive"
ClinGen's Dilated Cardiomyopathy Gene Curation Expert Panel classifies the MYH7-dilated cardiomyopathy relationship as Definitive with autosomal dominant inheritance.
PMID:11106718 SUPPORT Human Clinical
"Analyses of this and other genes for sarcomere proteins identified disease-causing dominant mutations in four kindreds."
Documents the dominant transmission of the sarcomeric dilated cardiomyopathy alleles, including the MYH7 alleles, in the founding kindreds.
⚙

Pathophysiology

4
MYH7 Missense Variant Causing Diminished Contractile Function
The initiating lesion in CMD1S is a heterozygous missense variant in MYH7, encoding the beta-cardiac myosin heavy chain. The founding alleles were Ser532Pro and Phe764Leu, identified after a genome-wide linkage study mapped a dilated cardiomyopathy locus to chromosome 14q11.2-13, where MYH7 is encoded. Unlike the hypertrophic MYH7 alleles curated in CMH1, which increase contractile output, the dilated alleles diminish contractile function - the same motor protein perturbed in the opposite functional direction.
Cardiomyocyte CL:0000746 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Cardiomyocyte, annotated with cardiac muscle cell (CL:0000746). CL:0000746 is a cell type from the Cell Ontology.
MYH7 hgnc:7577 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves MYH7 (hgnc:7577). hgnc:7577 is a gene from the HUGO Gene Nomenclature Committee.
Sarcomere Organization GO:0045214 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves abnormal Sarcomere Organization (GO:0045214). GO:0045214 is a biological process from the Gene Ontology. ⚠ ABNORMAL
Myosin thick filament GO:0032982 Gene Ontology (GO) Relation: this pathophysiological event involves this cellular component This pathophysiological event involves Myosin thick filament, annotated with myosin filament (GO:0032982). GO:0032982 is a cellular component from the Gene Ontology.
Downstream
Impaired Force Generation by the Sarcomere The mutant motor, incorporated into the thick filament, generates or transmits less force than wild-type myosin.
Show evidence (2 references)
PMID:11106718 SUPPORT Human Clinical
"A genetic locus for mutations associated with dilated cardiomyopathy was identified at chromosome 14q11.2-13 (maximal lod score, 5.11; theta=0), where the gene for cardiac beta-myosin heavy chain is encoded."
Documents the linkage mapping that identified MYH7 as the causal gene for this dilated cardiomyopathy entity.
PMID:11106718 SUPPORT Human Clinical
"Cardiac beta-myosin heavy-chain missense mutations (Ser532Pro and Phe764Leu) and a deletion in cardiac troponin T (deltaLys210) caused early-onset ventricular dilatation (average age at diagnosis, 24 years) and diminished contractile function and frequently resulted in heart failure."
Names the founding MYH7 dilated cardiomyopathy alleles and states their functional consequence - diminished contractile function with early-onset dilatation.
Impaired Force Generation by the Sarcomere
The mutant beta-myosin is expressed and incorporated into the sarcomere, where it degrades the contractile output of the cardiomyocyte rather than enhancing it. This hypocontractile lesion is the functional inverse of the hypertrophic MYH7 alleles, and it is the reason the ventricle responds by dilating rather than by thickening: the myocardium compensates for inadequate force by enlarging the chamber, not by adding wall thickness. Affected individuals accordingly show no antecedent hypertrophy and none of the histopathological features characteristic of hypertrophic disease.
Cardiomyocyte CL:0000746 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Cardiomyocyte, annotated with cardiac muscle cell (CL:0000746). CL:0000746 is a cell type from the Cell Ontology.
Muscle Contraction GO:0006936 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased Muscle Contraction (GO:0006936). GO:0006936 is a biological process from the Gene Ontology. ↓ DECREASED Cardiac Muscle Cell Contraction GO:0086003 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased Cardiac Muscle Cell Contraction (GO:0086003). GO:0086003 is a biological process from the Gene Ontology. ↓ DECREASED
Downstream
Ventricular Dilation and Systolic Dysfunction Chronic inadequate force generation drives chamber enlargement and falling systolic performance.
Show evidence (2 references)
PMID:11106718 SUPPORT Human Clinical
"Affected persons had neither antecedent cardiac hypertrophy (average maximal left-ventricular-wall thickness, 8.5 mm) nor histopathological findings characteristic of hypertrophy."
Establishes that the dilated MYH7 phenotype arises without a preceding hypertrophic phase and without hypertrophic histopathology, distinguishing it from CMH1 at the tissue level.
PMID:11106718 SUPPORT Human Clinical
"Because distinct mutations in sarcomere proteins cause either dilated or hypertrophic cardiomyopathy, the effects of mutant sarcomere proteins on muscle mechanics must trigger two different series of events that remodel the heart"
States the principle this entry exists to record: one sarcomere protein, two opposite remodelling programmes depending on the allele.
Ventricular Dilation and Systolic Dysfunction
Sustained hypocontractility produces the defining structural remodeling of dilated cardiomyopathy: left ventricular chamber enlargement with wall thinning, myocyte loss and interstitial fibrosis, with falling ejection fraction. In CMD1S this occurs early - the founding kindreds averaged 24 years at diagnosis - and without the myocyte disarray and wall thickening of the hypertrophic MYH7 phenotype.
Cardiomyocyte CL:0000746 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Cardiomyocyte, annotated with cardiac muscle cell (CL:0000746). CL:0000746 is a cell type from the Cell Ontology. Cardiac Fibroblast CL:0002548 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Cardiac Fibroblast, annotated with fibroblast of cardiac tissue (CL:0002548). CL:0002548 is a cell type from the Cell Ontology.
Heart Contraction GO:0060047 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased Heart Contraction (GO:0060047). GO:0060047 is a biological process from the Gene Ontology. ↓ DECREASED Extracellular Matrix Organization GO:0030198 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased Extracellular Matrix Organization (GO:0030198). GO:0030198 is a biological process from the Gene Ontology. ↑ INCREASED
Left ventricle UBERON:0002084 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in Left ventricle, annotated with heart left ventricle (UBERON:0002084). UBERON:0002084 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Heart Failure
Show evidence (1 reference)
PMID:11106718 SUPPORT Human Clinical
"Cardiac beta-myosin heavy-chain missense mutations (Ser532Pro and Phe764Leu) and a deletion in cardiac troponin T (deltaLys210) caused early-onset ventricular dilatation (average age at diagnosis, 24 years) and diminished contractile function and frequently resulted in heart failure."
Documents the early-onset ventricular dilatation with diminished contractile function that constitutes this node.
Heart Failure
The dilated, hypocontractile ventricle produces progressive systolic heart failure, which in the founding kindreds was a frequent outcome. Management follows standard heart-failure therapy, with transplantation for advanced refractory disease.
Cardiomyocyte CL:0000746 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Cardiomyocyte, annotated with cardiac muscle cell (CL:0000746). CL:0000746 is a cell type from the Cell Ontology.
Heart Contraction GO:0060047 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves abnormal Heart Contraction (GO:0060047). GO:0060047 is a biological process from the Gene Ontology. ⚠ ABNORMAL
Show evidence (1 reference)
PMID:11106718 SUPPORT Human Clinical
"diminished contractile function and frequently resulted in heart failure"
Documents heart failure as the frequent clinical outcome of the sarcomeric dilated cardiomyopathy alleles including MYH7.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Dilated Cardiomyopathy 1S Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

2
Dilated Cardiomyopathy OBLIGATE Cardiovascular HP:0001644 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Dilated cardiomyopathy (HP:0001644). HP:0001644 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:11106718 SUPPORT Human Clinical
"Cardiac beta-myosin heavy-chain missense mutations (Ser532Pro and Phe764Leu) and a deletion in cardiac troponin T (deltaLys210) caused early-onset ventricular dilatation (average age at diagnosis, 24 years) and diminished contractile function and frequently resulted in heart failure."
Establishes ventricular dilatation as the phenotype caused by the MYH7 dilated-cardiomyopathy alleles.
Congestive Heart Failure Cardiovascular HP:0001635 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Congestive heart failure (HP:0001635). HP:0001635 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:11106718 SUPPORT Human Clinical
"diminished contractile function and frequently resulted in heart failure"
Documents heart failure as a frequent outcome of this entity.
🧬

Genetic Associations

1
MYH7
Gene: MYH7 hgnc:7577 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is MYH7 (hgnc:7577). hgnc:7577 is a gene from the HUGO Gene Nomenclature Committee. relationship_type: CAUSATIVE
Show evidence (3 references)
CGGV:assertion_4ec27d4f-70ea-4c6a-ad67-d6260ecadcde-2025-05-30T160000.000Z SUPPORT Other
"MYH7 | HGNC:7577 | dilated cardiomyopathy | MONDO:0005021 | AD | Definitive"
ClinGen's Gene Curation Expert Panel classifies this gene-disease relationship as Definitive, which is the authority for curating the gene as CAUSATIVE rather than a candidate.
PMID:11106718 SUPPORT Human Clinical
"Analyses of this and other genes for sarcomere proteins identified disease-causing dominant mutations in four kindreds."
Establishes dominant sarcomere-protein mutations, MYH7 among them, as disease-causing in dilated cardiomyopathy kindreds.
PMID:11106718 SUPPORT Human Clinical
"Mutations in sarcomere protein genes account for approximately 10 percent of cases of familial dilated cardiomyopathy and are particularly prevalent in families with early-onset ventricular dilatation and dysfunction."
The 10% figure is measured over sarcomere protein genes as a class, not over MYH7. Curated PARTIAL for that reason: it bounds the MYH7 share from above but must not be quoted as the MYH7 case fraction, which is why no case_fractions record is recorded here. Note also that the same gene's hypertrophic-cardiomyopathy share, around 40%, belongs to a different disease and cannot be carried across.
💊

Medical Actions

2
Heart Failure Pharmacotherapy
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Standard guideline-directed heart-failure therapy targeting the neurohormonal drive of adverse remodeling.
Heart Transplantation
Action: organ transplantationNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is organ transplantation (NCIT:C15289). NCIT:C15289 is a clinical intervention from the NCI Thesaurus. Ontology label: Organ Transplantation NCIT:C15289
Advanced, refractory disease is an indication for transplantation.
📊

Prevalence

1
Familial dilated cardiomyopathy
Unknown Unknown
Sarcomere protein gene mutations collectively account for roughly 10% of familial dilated cardiomyopathy, of which MYH7 is one contributor; no population rate is established for the MYH7-specific entity.
Show evidence (1 reference)
PMID:11106718 SUPPORT Human Clinical
"Mutations in sarcomere protein genes account for approximately 10 percent of cases of familial dilated cardiomyopathy and are particularly prevalent in families with early-onset ventricular dilatation and dysfunction."
Gives the collective share of familial dilated cardiomyopathy attributable to sarcomere protein genes, the class to which MYH7 belongs, and notes the early-onset enrichment.
{ }

Source YAML

click to show 
name: Dilated Cardiomyopathy 1S
creation_date: "2026-08-23T00:00:00Z"
synonyms:
- CMD1S
- MYH7 familial isolated dilated cardiomyopathy
- dilated cardiomyopathy type 1S
- cardiomyopathy, dilated, 1S
- beta-myosin heavy chain dilated cardiomyopathy
description: >-
  Dilated cardiomyopathy 1S (CMD1S) is the MYH7-related form of familial isolated
  dilated cardiomyopathy. MYH7 encodes the beta-cardiac myosin heavy chain, the
  force-generating motor of the thick filament - the same protein whose variants
  cause hypertrophic cardiomyopathy 1 (CMH1). CMD1S is therefore the cleanest
  illustration in the knowledge base of a principle that the founding study of
  sarcomeric dilated cardiomyopathy set out explicitly: distinct mutations in one
  sarcomere protein cause either dilated or hypertrophic disease, so the mutant
  motor must trigger two different remodelling programmes. Where hypertrophic MYH7
  alleles act by a gain of contractile function, the dilated alleles diminish
  contractile function. Kamisago and colleagues established the entity in 2000 by
  mapping a dilated cardiomyopathy locus to 14q11.2-13, where MYH7 is encoded, and
  identifying dominant missense alleles (Ser532Pro, Phe764Leu) that produced
  early-onset ventricular dilatation with diminished contractile function and no
  antecedent hypertrophy. ClinGen classifies the MYH7-dilated cardiomyopathy
  relationship as Definitive with autosomal dominant inheritance.
category: Genetic
classifications:
  harrisons_chapter:
  - classification_value: CARDIOVASCULAR
  - classification_value: GENETICS_ENVIRONMENT_DISEASE
disease_term:
  preferred_term: dilated cardiomyopathy 1S
  term:
    id: MONDO:0013262
    label: dilated cardiomyopathy 1S
parents:
- Dilated Cardiomyopathy
- Genetic Disorder
inheritance:
- name: Autosomal dominant
  description: >-
    CMD1S is inherited as an autosomal dominant trait; a single MYH7 missense
    allele causes disease. Onset is characteristically early - the founding kindreds
    averaged 24 years at diagnosis - which is one of the features distinguishing
    sarcomeric from non-sarcomeric familial dilated cardiomyopathy.
  inheritance_term:
    preferred_term: Autosomal dominant inheritance
    term:
      id: HP:0000006
      label: Autosomal dominant inheritance
  penetrance: INCOMPLETE
  evidence:
  - reference: CGGV:assertion_4ec27d4f-70ea-4c6a-ad67-d6260ecadcde-2025-05-30T160000.000Z
    reference_title: "MYH7 / dilated cardiomyopathy (Definitive)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "MYH7 | HGNC:7577 | dilated cardiomyopathy | MONDO:0005021 | AD | Definitive"
    explanation: >-
      ClinGen's Dilated Cardiomyopathy Gene Curation Expert Panel classifies the
      MYH7-dilated cardiomyopathy relationship as Definitive with autosomal
      dominant inheritance.
  - reference: PMID:11106718
    reference_title: "Mutations in sarcomere protein genes as a cause of dilated cardiomyopathy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Analyses of this and other genes for sarcomere proteins identified
      disease-causing dominant mutations in four kindreds.
    explanation: >-
      Documents the dominant transmission of the sarcomeric dilated cardiomyopathy
      alleles, including the MYH7 alleles, in the founding kindreds.
prevalence:
- population: Familial dilated cardiomyopathy
  measure_type: UNKNOWN
  prevalence_class: UNKNOWN
  notes: >-
    Sarcomere protein gene mutations collectively account for roughly 10% of
    familial dilated cardiomyopathy, of which MYH7 is one contributor; no
    population rate is established for the MYH7-specific entity.
  evidence:
  - reference: PMID:11106718
    reference_title: "Mutations in sarcomere protein genes as a cause of dilated cardiomyopathy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Mutations in sarcomere protein genes account for approximately 10 percent of
      cases of familial dilated cardiomyopathy and are particularly prevalent in
      families with early-onset ventricular dilatation and dysfunction.
    explanation: >-
      Gives the collective share of familial dilated cardiomyopathy attributable to
      sarcomere protein genes, the class to which MYH7 belongs, and notes the
      early-onset enrichment.
pathophysiology:
- name: MYH7 Missense Variant Causing Diminished Contractile Function
  biological_scale: MOLECULAR
  role: trigger
  conforms_to: "cardiomyopathy_maladaptive_remodeling#Primary Cardiomyocyte Insult"
  description: >-
    The initiating lesion in CMD1S is a heterozygous missense variant in MYH7,
    encoding the beta-cardiac myosin heavy chain. The founding alleles were
    Ser532Pro and Phe764Leu, identified after a genome-wide linkage study mapped a
    dilated cardiomyopathy locus to chromosome 14q11.2-13, where MYH7 is encoded.
    Unlike the hypertrophic MYH7 alleles curated in CMH1, which increase
    contractile output, the dilated alleles diminish contractile function - the same
    motor protein perturbed in the opposite functional direction.
  genes:
  - preferred_term: MYH7
    term:
      id: hgnc:7577
      label: MYH7
  cell_types:
  - preferred_term: Cardiomyocyte
    term:
      id: CL:0000746
      label: cardiac muscle cell
  biological_processes:
  - preferred_term: Sarcomere Organization
    term:
      id: GO:0045214
      label: sarcomere organization
    modifier: ABNORMAL
  cellular_components:
  - preferred_term: Myosin thick filament
    term:
      id: GO:0032982
      label: myosin filament
  evidence:
  - reference: PMID:11106718
    reference_title: "Mutations in sarcomere protein genes as a cause of dilated cardiomyopathy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      A genetic locus for mutations associated with dilated cardiomyopathy was
      identified at chromosome 14q11.2-13 (maximal lod score, 5.11; theta=0), where
      the gene for cardiac beta-myosin heavy chain is encoded.
    explanation: >-
      Documents the linkage mapping that identified MYH7 as the causal gene for this
      dilated cardiomyopathy entity.
  - reference: PMID:11106718
    reference_title: "Mutations in sarcomere protein genes as a cause of dilated cardiomyopathy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Cardiac beta-myosin heavy-chain missense mutations (Ser532Pro and Phe764Leu)
      and a deletion in cardiac troponin T (deltaLys210) caused early-onset
      ventricular dilatation (average age at diagnosis, 24 years) and diminished
      contractile function and frequently resulted in heart failure.
    explanation: >-
      Names the founding MYH7 dilated cardiomyopathy alleles and states their
      functional consequence - diminished contractile function with early-onset
      dilatation.
  downstream:
  - target: Impaired Force Generation by the Sarcomere
    causal_link_type: DIRECT
    description: >-
      The mutant motor, incorporated into the thick filament, generates or transmits
      less force than wild-type myosin.
- name: Impaired Force Generation by the Sarcomere
  biological_scale: MOLECULAR
  role: effector
  description: >-
    The mutant beta-myosin is expressed and incorporated into the sarcomere, where
    it degrades the contractile output of the cardiomyocyte rather than enhancing
    it. This hypocontractile lesion is the functional inverse of the hypertrophic
    MYH7 alleles, and it is the reason the ventricle responds by dilating rather
    than by thickening: the myocardium compensates for inadequate force by
    enlarging the chamber, not by adding wall thickness. Affected individuals
    accordingly show no antecedent hypertrophy and none of the histopathological
    features characteristic of hypertrophic disease.
  cell_types:
  - preferred_term: Cardiomyocyte
    term:
      id: CL:0000746
      label: cardiac muscle cell
  biological_processes:
  - preferred_term: Muscle Contraction
    term:
      id: GO:0006936
      label: muscle contraction
    modifier: DECREASED
  - preferred_term: Cardiac Muscle Cell Contraction
    term:
      id: GO:0086003
      label: cardiac muscle cell contraction
    modifier: DECREASED
  evidence:
  - reference: PMID:11106718
    reference_title: "Mutations in sarcomere protein genes as a cause of dilated cardiomyopathy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Affected persons had neither antecedent cardiac hypertrophy (average maximal
      left-ventricular-wall thickness, 8.5 mm) nor histopathological findings
      characteristic of hypertrophy.
    explanation: >-
      Establishes that the dilated MYH7 phenotype arises without a preceding
      hypertrophic phase and without hypertrophic histopathology, distinguishing it
      from CMH1 at the tissue level.
  - reference: PMID:11106718
    reference_title: "Mutations in sarcomere protein genes as a cause of dilated cardiomyopathy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Because distinct mutations in sarcomere proteins cause either dilated or
      hypertrophic cardiomyopathy, the effects of mutant sarcomere proteins on
      muscle mechanics must trigger two different series of events that remodel the
      heart
    explanation: >-
      States the principle this entry exists to record: one sarcomere protein, two
      opposite remodelling programmes depending on the allele.
  downstream:
  - target: Ventricular Dilation and Systolic Dysfunction
    causal_link_type: DIRECT
    description: >-
      Chronic inadequate force generation drives chamber enlargement and falling
      systolic performance.
- name: Ventricular Dilation and Systolic Dysfunction
  biological_scale: TISSUE
  role: central_effector
  conforms_to: "cardiomyopathy_maladaptive_remodeling#Ventricular Remodeling"
  description: >-
    Sustained hypocontractility produces the defining structural remodeling of
    dilated cardiomyopathy: left ventricular chamber enlargement with wall thinning,
    myocyte loss and interstitial fibrosis, with falling ejection fraction. In
    CMD1S this occurs early - the founding kindreds averaged 24 years at diagnosis -
    and without the myocyte disarray and wall thickening of the hypertrophic MYH7
    phenotype.
  cell_types:
  - preferred_term: Cardiomyocyte
    term:
      id: CL:0000746
      label: cardiac muscle cell
  - preferred_term: Cardiac Fibroblast
    term:
      id: CL:0002548
      label: fibroblast of cardiac tissue
  biological_processes:
  - preferred_term: Heart Contraction
    term:
      id: GO:0060047
      label: heart contraction
    modifier: DECREASED
  - preferred_term: Extracellular Matrix Organization
    term:
      id: GO:0030198
      label: extracellular matrix organization
    modifier: INCREASED
  locations:
  - preferred_term: Left ventricle
    term:
      id: UBERON:0002084
      label: heart left ventricle
  evidence:
  - reference: PMID:11106718
    reference_title: "Mutations in sarcomere protein genes as a cause of dilated cardiomyopathy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Cardiac beta-myosin heavy-chain missense mutations (Ser532Pro and Phe764Leu)
      and a deletion in cardiac troponin T (deltaLys210) caused early-onset
      ventricular dilatation (average age at diagnosis, 24 years) and diminished
      contractile function and frequently resulted in heart failure.
    explanation: >-
      Documents the early-onset ventricular dilatation with diminished contractile
      function that constitutes this node.
  downstream:
  - target: Heart Failure
    causal_link_type: DIRECT
- name: Heart Failure
  biological_scale: ORGANISM
  role: consequence
  conforms_to: "cardiomyopathy_maladaptive_remodeling#Structural Cardiac Impairment and Heart Failure"
  description: >-
    The dilated, hypocontractile ventricle produces progressive systolic heart
    failure, which in the founding kindreds was a frequent outcome. Management
    follows standard heart-failure therapy, with transplantation for advanced
    refractory disease.
  cell_types:
  - preferred_term: Cardiomyocyte
    term:
      id: CL:0000746
      label: cardiac muscle cell
  biological_processes:
  - preferred_term: Heart Contraction
    term:
      id: GO:0060047
      label: heart contraction
    modifier: ABNORMAL
  evidence:
  - reference: PMID:11106718
    reference_title: "Mutations in sarcomere protein genes as a cause of dilated cardiomyopathy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      diminished contractile function and frequently resulted in heart failure
    explanation: >-
      Documents heart failure as the frequent clinical outcome of the sarcomeric
      dilated cardiomyopathy alleles including MYH7.
phenotypes:
- name: Dilated Cardiomyopathy
  category: Cardiovascular
  description: >-
    Left ventricular dilation with systolic dysfunction, without antecedent
    hypertrophy, is the defining feature of CMD1S.
  phenotype_term:
    preferred_term: Dilated cardiomyopathy
    term:
      id: HP:0001644
      label: Dilated cardiomyopathy
  frequency: OBLIGATE
  evidence:
  - reference: PMID:11106718
    reference_title: "Mutations in sarcomere protein genes as a cause of dilated cardiomyopathy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Cardiac beta-myosin heavy-chain missense mutations (Ser532Pro and Phe764Leu)
      and a deletion in cardiac troponin T (deltaLys210) caused early-onset
      ventricular dilatation (average age at diagnosis, 24 years) and diminished
      contractile function and frequently resulted in heart failure.
    explanation: >-
      Establishes ventricular dilatation as the phenotype caused by the MYH7
      dilated-cardiomyopathy alleles.
- name: Congestive Heart Failure
  category: Cardiovascular
  description: >-
    Progressive systolic dysfunction produces heart failure, a frequent outcome in
    the founding kindreds.
  phenotype_term:
    preferred_term: Congestive heart failure
    term:
      id: HP:0001635
      label: Congestive heart failure
  evidence:
  - reference: PMID:11106718
    reference_title: "Mutations in sarcomere protein genes as a cause of dilated cardiomyopathy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      diminished contractile function and frequently resulted in heart failure
    explanation: >-
      Documents heart failure as a frequent outcome of this entity.
genetic:
- name: MYH7
  gene_term:
    preferred_term: MYH7
    term:
      id: hgnc:7577
      label: MYH7
  relationship_type: CAUSATIVE
  frequency: >-
    Minority cause of familial dilated cardiomyopathy. Sarcomere protein genes
    as a class account for roughly 10% of familial cases; MYH7 is one
    contributor to that class and no MYH7-specific dilated-cardiomyopathy
    share has been reported.
  evidence:
  - reference: CGGV:assertion_4ec27d4f-70ea-4c6a-ad67-d6260ecadcde-2025-05-30T160000.000Z
    reference_title: "MYH7 / dilated cardiomyopathy (Definitive)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      MYH7 | HGNC:7577 | dilated cardiomyopathy | MONDO:0005021 | AD |
      Definitive
    explanation: >-
      ClinGen's Gene Curation Expert Panel classifies this gene-disease
      relationship as Definitive, which is the authority for curating the gene
      as CAUSATIVE rather than a candidate.
  - reference: PMID:11106718
    reference_title: "Mutations in sarcomere protein genes as a cause of dilated cardiomyopathy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Analyses of this and other genes for sarcomere proteins identified
      disease-causing dominant mutations in four kindreds.
    explanation: >-
      Establishes dominant sarcomere-protein mutations, MYH7 among them, as
      disease-causing in dilated cardiomyopathy kindreds.
  - reference: PMID:11106718
    reference_title: "Mutations in sarcomere protein genes as a cause of dilated cardiomyopathy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Mutations in sarcomere protein genes account for approximately 10
      percent of cases of familial dilated cardiomyopathy and are particularly
      prevalent in families with early-onset ventricular dilatation and
      dysfunction.
    explanation: >-
      The 10% figure is measured over sarcomere protein genes as a class, not
      over MYH7. Curated PARTIAL for that reason: it bounds the MYH7 share
      from above but must not be quoted as the MYH7 case fraction, which is
      why no case_fractions record is recorded here. Note also that the same
      gene's hypertrophic-cardiomyopathy share, around 40%, belongs to a
      different disease and cannot be carried across.
treatments:
- name: Heart Failure Pharmacotherapy
  description: >-
    Standard guideline-directed heart-failure therapy targeting the neurohormonal
    drive of adverse remodeling.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
- name: Heart Transplantation
  description: >-
    Advanced, refractory disease is an indication for transplantation.
  therapeutic_modality: SURGERY
  treatment_term:
    preferred_term: organ transplantation
    term:
      id: NCIT:C15289
      label: Organ Transplantation
references:
- reference: PMID:20301486
  title: Dilated Cardiomyopathy Overview.
  tags:
  - GeneReviews
notes: >-
  CMD1S is the MYH7 member of the numbered dilated cardiomyopathy series and
  carries ClinGen Definitive gene-disease validity. It conforms to the shared
  cardiomyopathy_maladaptive_remodeling module.

  The reason this entry earns its place alongside Hypertrophic Cardiomyopathy 1 is
  the allelic contrast, which is curated explicitly rather than left implicit: one
  gene, one protein, two opposite remodelling programmes. CMH1 alleles act by a
  gain of contractile function (super-relaxed-state destabilization, raised
  intrinsic force); CMD1S alleles diminish contractile function and the ventricle
  dilates instead of thickening. The founding study states the principle directly,
  and that statement is curated as evidence on the effector node.

  Scope caveat. The entry deliberately does not assert a single settled
  structural rule (for example a head-domain versus rod-domain partition) for which
  MYH7 alleles give dilated rather than hypertrophic disease; the founding alleles
  are cited by name and the functional direction is what is claimed. Sharpening
  that genotype-structure relationship is a natural augmentation if the literature
  supports it.

  GeneReviews scope. The GeneReviews resource applicable to this entry is the
  disease-level "Dilated Cardiomyopathy Overview" (PMID:20301486), tagged
  accordingly in `references`. Its indexed PubMed record is content_type
  abstract_only and carries only the chapter's purpose statement, not the
  Clinical Characteristics, Management, or Genetic Counseling sections, so
  section-by-section GeneReviews mining is not possible from the cache and no
  snippet is quoted from it. The clinical-characteristics baseline for this
  entry is therefore built from the primary MYH7 cohort and pedigree literature
  cited throughout, principally PMID:11106718.
📚

References & Deep Research

References

1
PMID:20301486
Dilated Cardiomyopathy Overview.
No top-level findings curated for this source.