MYH7
myosin heavy chain 7, the group of MicroRNA protein coding host genes|Myosin heavy chains, class II
Basic information
Region (hg38): 14:23412740-23435660
Previous symbols: [ "CMH1", "MPD1" ]
Links
Phenotypes
GenCC
Source:
- hypertrophic cardiomyopathy 1 (Strong), mode of inheritance: AD
- myopathy, myosin storage, autosomal dominant (Moderate), mode of inheritance: AD
- dilated cardiomyopathy 1S (Strong), mode of inheritance: AD
- myopathy, myosin storage, autosomal recessive (Moderate), mode of inheritance: AR
- hypertrophic cardiomyopathy 1 (Definitive), mode of inheritance: AD
- MYH7-related skeletal myopathy (Strong), mode of inheritance: AD
- Ebstein anomaly (Supportive), mode of inheritance: AD
- familial isolated dilated cardiomyopathy (Supportive), mode of inheritance: AD
- hyaline body myopathy (Supportive), mode of inheritance: AD
- left ventricular noncompaction (Supportive), mode of inheritance: AD
- MYH7-related skeletal myopathy (Supportive), mode of inheritance: AD
- congenital myopathy 7A, myosin storage, autosomal dominant (Supportive), mode of inheritance: AD
- myopathy, myosin storage, autosomal recessive (Strong), mode of inheritance: AR
- dilated cardiomyopathy 1S (Definitive), mode of inheritance: AD
- hypertrophic cardiomyopathy 1 (Definitive), mode of inheritance: AD
- dilated cardiomyopathy 1S (Strong), mode of inheritance: AD
- MYH7-related skeletal myopathy (Strong), mode of inheritance: AD
- hypertrophic cardiomyopathy 1 (Strong), mode of inheritance: AD
- arrhythmogenic right ventricular cardiomyopathy (Limited), mode of inheritance: AD
- hypertrophic cardiomyopathy (Definitive), mode of inheritance: AD
- dilated cardiomyopathy (Definitive), mode of inheritance: AD
- MYH7-related skeletal myopathy (Definitive), mode of inheritance: AD
- congenital heart disease (Limited), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Cardiomyopathy, dilated, 1S; Cardiomyopathy, familial hypertrophic 1; Myopathy, distal; Congenital myopathy 7B, myosin storage, autosomal recessive | AD/AR | Cardiovascular | Individuals can have cardiovascular anomalies, including dilated cardiomyopathy, hypertrophic cardiomyopathy, and arrhythmias, and surveillance and early treatment may be beneficial | Cardiovascular; Musculoskeletal | 13732753; 4104682; 1975517; 1361491; 1552912; 8254035; 8483915; 8343162; 8282798; 7909436; 8655135; 9544842; 10521296; 10424815; 11106718; 11102913; 11424919; 11733062; 11166161; 12379228; 14663035; 12975303; 12749056; 14520662; 14659406; 15136674; 15322983; 16267253; 15483641; 15699387; 16684601; 16650083; 17372140; 17548557; 17476457; 17336526; 18175163; 18506004; 19026577; 19138847; 19336582; 20503496; 20733148; 21395566; 21896538; 23117287; 23478172; 23956225; 25666907 |
| Compound heterozygosity and digenic inheritance (with MYLK2) has been described as an explanation for severe manifestations in some individuals |
ClinVar
This is a list of variants' phenotypes submitted to
- Hypertrophic_cardiomyopathy (3725 variants)
- Cardiomyopathy (2091 variants)
- Cardiovascular_phenotype (1448 variants)
- not_provided (1442 variants)
- not_specified (728 variants)
- Hypertrophic_cardiomyopathy_1 (547 variants)
- Dilated_cardiomyopathy_1S (395 variants)
- Myosin_storage_myopathy (390 variants)
- MYH7-related_skeletal_myopathy (379 variants)
- Myopathy,_myosin_storage,_autosomal_recessive (249 variants)
- Congenital_myopathy_with_fiber_type_disproportion (216 variants)
- MYH7-related_disorder (147 variants)
- Primary_dilated_cardiomyopathy (84 variants)
- Left_ventricular_noncompaction_cardiomyopathy (81 variants)
- Primary_familial_hypertrophic_cardiomyopathy (78 variants)
- Dilated_Cardiomyopathy,_Dominant (58 variants)
- Familial_cardiomyopathy (36 variants)
- See_cases (13 variants)
- Left_ventricular_noncompaction (12 variants)
- Scapuloperoneal_myopathy (10 variants)
- Inborn_genetic_diseases (7 variants)
- Left_ventricular_noncompaction_5 (7 variants)
- Primary_familial_dilated_cardiomyopathy (6 variants)
- Restrictive_cardiomyopathy (6 variants)
- Wolff-Parkinson-White_pattern (4 variants)
- Long_QT_syndrome (3 variants)
- Congenital_myopathy (3 variants)
- Hypertrophic_cardiomyopathy_2 (3 variants)
- Conduction_disorder_of_the_heart (2 variants)
- Biventricular_noncompaction_cardiomyopathy (2 variants)
- Ventricular_fibrillation (2 variants)
- Arrhythmogenic_cardiomyopathy (2 variants)
- Hyaline_body_myopathy (2 variants)
- Sudden_unexplained_death (2 variants)
- Left_ventricular_noncompaction_1 (2 variants)
- Arrhythmogenic_right_ventricular_cardiomyopathy (2 variants)
- Myopathy (2 variants)
- Dilated_cardiomyopathy_1A (1 variants)
- Distal_muscle_weakness (1 variants)
- Ebstein_anomaly (1 variants)
- Left_ventricular_hypertrophy (1 variants)
- Sagittal_craniosynostosis (1 variants)
- Asymmetric_septal_hypertrophy (1 variants)
- Delayed_speech_and_language_development (1 variants)
- Cardiac_arrhythmia (1 variants)
- Craniosynostosis_4 (1 variants)
- Pericarditis (1 variants)
- Abnormality_of_the_musculature (1 variants)
- Delayed_gross_motor_development (1 variants)
- Exertional_Heat_Illness (1 variants)
- Congenital_muscular_dystrophy (1 variants)
- Cardiomyopathy,_hypertrophic,_midventricular,_digenic (1 variants)
- Muscular_ventricular_septal_defect (1 variants)
- Neuromuscular_disease (1 variants)
- Familial_isolated_arrhythmogenic_right_ventricular_dysplasia (1 variants)
- First_degree_atrioventricular_block (1 variants)
- MYH7-related_cardiomyopathy (1 variants)
- Neuromuscular_disease_caused_by_qualitative_or_quantitative_defects_of_beta-myosin_heavy_chain_(MYH7) (1 variants)
- Epicanthus (1 variants)
- Sudden_cardiac_death (1 variants)
- Hypotonia (1 variants)
- Dyspnea (1 variants)
- Prolonged_QT_interval (1 variants)
- Autosomal_dominant_MYH7-related_disorder (1 variants)
- Increased_left_ventricular_wall_thickness (1 variants)
- Hypertrophic_cardiomyopathy_4 (1 variants)
- Atrial_flutter (1 variants)
- Idiopathic_camptocormia (1 variants)
- Chest_pain (1 variants)
- Atrial_fibrillation (1 variants)
- Heart_failure (1 variants)
- Myocarditis (1 variants)
- Ventricular_tachycardia (1 variants)
- Limb-girdle_muscular_dystrophy (1 variants)
- Tachycardia (1 variants)
- Arrhythmogenic_right_ventricular_dysplasia_9 (1 variants)
- Polymorphic_ventricular_tachycardia (1 variants)
- Abnormal_morphology_of_left_ventricular_trabeculae (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the MYH7 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000257.4. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 31 | 1057 | 45 | 1135 | ||
| missense | 88 | 521 | 2280 | 39 | 2933 | |
| nonsense | 83 | 91 | ||||
| start loss | 2 | 2 | ||||
| frameshift | 117 | 128 | ||||
| splice donor/acceptor (+/-2bp) | 14 | 77 | 99 | |||
| Total | 99 | 551 | 2590 | 1096 | 52 |
Highest pathogenic variant AF is 0.00003593534
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| MYH7 | protein_coding | protein_coding | ENST00000355349 | 38 | 22981 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 4.24e-16 | 1.00 | 125654 | 0 | 94 | 125748 | 0.000374 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.93 | 742 | 1.11e+3 | 0.668 | 0.0000785 | 12819 |
| Missense in Polyphen | 344 | 594.93 | 0.57822 | 7096 | ||
| Synonymous | -2.91 | 552 | 472 | 1.17 | 0.0000336 | 3631 |
| Loss of Function | 5.05 | 43 | 96.5 | 0.446 | 0.00000524 | 1183 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000600 | 0.000596 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000163 | 0.000163 |
| Finnish | 0.000324 | 0.000323 |
| European (Non-Finnish) | 0.000485 | 0.000475 |
| Middle Eastern | 0.000163 | 0.000163 |
| South Asian | 0.000392 | 0.000392 |
| Other | 0.000489 | 0.000489 |
dbNSFP
Source:
- Function
- FUNCTION: Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction. Forms regular bipolar thick filaments that, together with actin thin filaments, constitute the fundamental contractile unit of skeletal and cardiac muscle. {ECO:0000305|PubMed:26150528, ECO:0000305|PubMed:26246073}.;
- Disease
- DISEASE: Cardiomyopathy, familial hypertrophic 1 (CMH1) [MIM:192600]: A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. {ECO:0000269|PubMed:10065021, ECO:0000269|PubMed:10329202, ECO:0000269|PubMed:10521296, ECO:0000269|PubMed:10563488, ECO:0000269|PubMed:10679957, ECO:0000269|PubMed:10862102, ECO:0000269|PubMed:11113006, ECO:0000269|PubMed:11133230, ECO:0000269|PubMed:11214007, ECO:0000269|PubMed:11424919, ECO:0000269|PubMed:11733062, ECO:0000269|PubMed:11861413, ECO:0000269|PubMed:11968089, ECO:0000269|PubMed:12081993, ECO:0000269|PubMed:12566107, ECO:0000269|PubMed:12590187, ECO:0000269|PubMed:12707239, ECO:0000269|PubMed:12818575, ECO:0000269|PubMed:12820698, ECO:0000269|PubMed:12951062, ECO:0000269|PubMed:12974739, ECO:0000269|PubMed:12975413, ECO:0000269|PubMed:1417858, ECO:0000269|PubMed:15358028, ECO:0000269|PubMed:15483641, ECO:0000269|PubMed:1552912, ECO:0000269|PubMed:15563892, ECO:0000269|PubMed:15856146, ECO:0000269|PubMed:15858117, ECO:0000269|PubMed:16199542, ECO:0000269|PubMed:16267253, ECO:0000269|PubMed:1638703, ECO:0000269|PubMed:16650083, ECO:0000269|PubMed:16938236, ECO:0000269|PubMed:17095604, ECO:0000269|PubMed:17372140, ECO:0000269|PubMed:18175163, ECO:0000269|PubMed:18403758, ECO:0000269|PubMed:1975517, ECO:0000269|PubMed:25182012, ECO:0000269|PubMed:7581410, ECO:0000269|PubMed:7731997, ECO:0000269|PubMed:7848441, ECO:0000269|PubMed:7874131, ECO:0000269|PubMed:8250038, ECO:0000269|PubMed:8254035, ECO:0000269|PubMed:8268932, ECO:0000269|PubMed:8282798, ECO:0000269|PubMed:8343162, ECO:0000269|PubMed:8435239, ECO:0000269|PubMed:8483915, ECO:0000269|PubMed:8655135, ECO:0000269|PubMed:8899546, ECO:0000269|PubMed:9544842, ECO:0000269|PubMed:9822100, ECO:0000269|PubMed:9829907}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Myopathy, myosin storage, autosomal dominant (MSMA) [MIM:608358]: A rare congenital myopathy characterized by subsarcolemmal hyalinized bodies in type 1 muscle fibers. {ECO:0000269|PubMed:14520662, ECO:0000269|PubMed:15136674, ECO:0000269|PubMed:16684601, ECO:0000269|PubMed:17336526}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Scapuloperoneal myopathy MYH7-related (SPMM) [MIM:181430]: Progressive muscular atrophia beginning in the lower legs and affecting the shoulder region earlier and more severely than distal arm. {ECO:0000269|PubMed:17336526}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cardiomyopathy, dilated 1S (CMD1S) [MIM:613426]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269|PubMed:11106718, ECO:0000269|PubMed:12379228, ECO:0000269|PubMed:15769782, ECO:0000269|PubMed:18506004, ECO:0000269|PubMed:21127202, ECO:0000269|PubMed:21846512}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Myopathy, distal, 1 (MPD1) [MIM:160500]: A muscular disorder characterized by early-onset selective weakness of the great toe and ankle dorsiflexors, followed by weakness of the finger extensors. Mild proximal weakness occasionally develops years later after the onset of the disease. {ECO:0000269|PubMed:15322983, ECO:0000269|PubMed:17548557}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Myopathy, myosin storage, autosomal recessive (MSMB) [MIM:255160]: An autosomal recessive form of myosin storage myopathy, a muscle disease characterized by subsarcolemmal accumulation of hyalinized bodies in type 1 muscle fibers. MSMB clinical features include muscle weakness, type II respiratory failure and cardiac failure, due to hypertrophic cardiomyopathy. {ECO:0000269|PubMed:25666907}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Left ventricular non-compaction 5 (LVNC5) [MIM:613426]: A form of left ventricular non-compaction, a cardiomyopathy due to myocardial morphogenesis arrest and characterized by a hypertrophic left ventricle, a severely thickened 2-layered myocardium, numerous prominent trabeculations, deep intertrabecular recesses, and poor systolic function. Clinical manifestations are variable. Some affected individuals experience no symptoms at all, others develop heart failure. In some cases, left ventricular non-compaction is associated with other congenital heart anomalies. LVNC5 is an autosomal dominant condition. {ECO:0000269|PubMed:18506004}. Note=The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry.;
- Pathway
- Cardiac muscle contraction - Homo sapiens (human);Dilated cardiomyopathy (DCM) - Homo sapiens (human);Viral myocarditis - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Striated Muscle Contraction;Muscle contraction
(Consensus)
Recessive Scores
- pRec
- 0.168
Intolerance Scores
- loftool
- 0.0412
- rvis_EVS
- -3.64
- rvis_percentile_EVS
- 0.28
Haploinsufficiency Scores
- pHI
- 0.439
- hipred
- Y
- hipred_score
- 0.632
- ghis
- 0.561
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.895
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Myh7
- Phenotype
- muscle phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan);
Zebrafish Information Network
- Gene name
- myh7
- Affected structure
- cardiac ventricle
- Phenotype tag
- abnormal
- Phenotype quality
- curvature
Gene ontology
- Biological process
- regulation of the force of heart contraction;regulation of heart rate;skeletal muscle contraction;muscle contraction;striated muscle contraction;adult heart development;regulation of the force of skeletal muscle contraction;transition between fast and slow fiber;cardiac muscle hypertrophy in response to stress;muscle filament sliding;regulation of slow-twitch skeletal muscle fiber contraction;ATP metabolic process;ventricular cardiac muscle tissue morphogenesis;cardiac muscle contraction
- Cellular component
- stress fiber;muscle myosin complex;myosin complex;myofibril;sarcomere;Z disc;myosin filament
- Molecular function
- microfilament motor activity;protein binding;calmodulin binding;ATP binding;ATPase activity;actin-dependent ATPase activity;actin filament binding