MYBPC3

myosin binding protein C3, the group of I-set domain containing|Myosin binding proteins

Basic information

Region (hg38): 11:47331406-47352702

Previous symbols: [ "CMH4" ]

Links

ENSG00000134571 ∙ NCBI:4607 ∙ OMIM:600958 ∙ HGNC:7551 ∙ Uniprot:Q14896 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• left ventricular noncompaction 10 (Definitive), mode of inheritance: AD
• hypertrophic cardiomyopathy 4 (Definitive), mode of inheritance: AD
• left ventricular noncompaction 10 (Moderate), mode of inheritance: AD
• familial isolated dilated cardiomyopathy (Supportive), mode of inheritance: AD
• hypertrophic cardiomyopathy 4 (Definitive), mode of inheritance: AD
• hypertrophic cardiomyopathy 4 (Strong), mode of inheritance: AD
• arrhythmogenic right ventricular cardiomyopathy (Limited), mode of inheritance: AD
• dilated cardiomyopathy (Limited), mode of inheritance: AD
• hypertrophic cardiomyopathy (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiomyopathy, familial hypertrophic, 4; Cardiomyopathy, dilated, 1MM; Left ventricular noncompaction 10	AD/AR	Cardiovascular	Surveillance in order to allow early diagnosis and treatment of cardiomyopathy can be beneficial; Cardiac transplantation has been described	Cardiovascular	7493026; 7493025; 9241277; 9562578; 10424815; 12788380; 15519027; 16199542; 16679492; 17655857; 17937428; 18337725; 19858127; 21839045; 22021246; 22314326; 22455086

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MYBPC3 gene.

• Hypertrophic cardiomyopathy (407 variants)
• not provided (185 variants)
• Cardiovascular phenotype (168 variants)
• Cardiomyopathy (92 variants)
• Hypertrophic cardiomyopathy 4 (64 variants)
• Primary familial hypertrophic cardiomyopathy (30 variants)
• Hypertrophic cardiomyopathy 1 (10 variants)
• Left ventricular noncompaction 10 (10 variants)
• MYBPC3-related disorder (8 variants)
• Left ventricular noncompaction 10;Hypertrophic cardiomyopathy 4 (8 variants)
• Hypertrophic cardiomyopathy 4;Left ventricular noncompaction 10 (7 variants)
• not specified (2 variants)
• Primary dilated cardiomyopathy (2 variants)
• Hypertrophic cardiomyopathy;Primary dilated cardiomyopathy (1 variants)
• Left ventricular noncompaction 1;Hypertrophic cardiomyopathy 4;Primary dilated cardiomyopathy (1 variants)
• Primary familial dilated cardiomyopathy (1 variants)
• Primary dilated cardiomyopathy;Left ventricular noncompaction 1;Hypertrophic cardiomyopathy 4 (1 variants)
• Left ventricular noncompaction (1 variants)
• SUDDEN INFANT DEATH SYNDROME (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MYBPC3 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			22	534	6	562
missense	3	29	1343	27	2	1404
nonsense	137	49				186
start loss						0
frameshift	324	123	1			448
inframe indel	2	3	41			46
splice donor/acceptor (+/-2bp)	64	98	5			167
splice region	1	11	121	92	1	226
non coding	1	7	60	311	59	438
Total	531	309	1472	872	67

Highest pathogenic variant AF is 0.0000591

Variants in MYBPC3

This is a list of pathogenic ClinVar variants found in the MYBPC3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-47331416-G-T		Dilated Cardiomyopathy, Dominant • Left ventricular noncompaction cardiomyopathy • Hypertrophic cardiomyopathy	Uncertain significance (Jun 14, 2016)
11-47331429-T-C			Benign (Mar 03, 2015)
11-47331449-A-T			Benign (Mar 03, 2015)
11-47331450-T-C		Left ventricular noncompaction 10 • Hypertrophic cardiomyopathy 4	Uncertain significance (Jan 13, 2018)
11-47331468-C-T		Hypertrophic cardiomyopathy 4 • Left ventricular noncompaction 10	Uncertain significance (Jan 13, 2018)
11-47331507-C-T		Hypertrophic cardiomyopathy 4 • Left ventricular noncompaction 10	Benign/Likely benign (Jan 13, 2018)
11-47331512-CT-C		Hypertrophic cardiomyopathy • Dilated Cardiomyopathy, Dominant • Left ventricular noncompaction cardiomyopathy	Benign/Likely benign (Jun 14, 2016)
11-47331531-G-C		Hypertrophic cardiomyopathy 4 • Left ventricular noncompaction 10	Uncertain significance (Jan 12, 2018)
11-47331580-G-T		Dilated Cardiomyopathy, Dominant • Hypertrophic cardiomyopathy • Left ventricular noncompaction cardiomyopathy	Uncertain significance (Jun 14, 2016)
11-47331612-A-G		Hypertrophic cardiomyopathy 4 • Left ventricular noncompaction 10	Conflicting classifications of pathogenicity (Jan 13, 2018)
11-47331616-C-T		Left ventricular noncompaction 10 • Hypertrophic cardiomyopathy 4	Uncertain significance (Jan 12, 2018)
11-47331624-G-T		Left ventricular noncompaction 10 • Hypertrophic cardiomyopathy 4	Uncertain significance (Jan 13, 2018)
11-47331627-A-G		Left ventricular noncompaction 10 • Hypertrophic cardiomyopathy 4	Uncertain significance (Jan 13, 2018)
11-47331630-C-A		Hypertrophic cardiomyopathy 4 • Left ventricular noncompaction 10	Benign/Likely benign (Jan 12, 2018)
11-47331648-C-A		Dilated Cardiomyopathy, Dominant • Hypertrophic cardiomyopathy • Left ventricular noncompaction cardiomyopathy	Uncertain significance (Jun 14, 2016)
11-47331696-G-A			Benign (Mar 03, 2015)
11-47331760-G-T			Benign (Jun 23, 2018)
11-47331829-G-C			Benign (Mar 03, 2015)
11-47331831-C-T		not specified	Benign (Oct 25, 2013)
11-47331832-G-A		not specified	Likely benign (Oct 20, 2015)
11-47331842-T-C		Left ventricular noncompaction cardiomyopathy • Dilated Cardiomyopathy, Dominant • Hypertrophic cardiomyopathy	Uncertain significance (Jun 14, 2016)
11-47331843-A-G			Uncertain significance (Apr 22, 2021)
11-47331844-C-T			Uncertain significance (Feb 09, 2024)
11-47331848-GCCATCCCCAGGAGCCAGCCTGGTC-G		Cardiovascular phenotype	Uncertain significance (Jun 16, 2016)
11-47331854-CCCAGGAGCCAG-C		not specified	Uncertain significance (Jan 02, 2009)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MYBPC3	protein_coding	protein_coding	ENST00000545968	34	21297

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.01e-11	1.00	124677	0	79	124756	0.000317

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.45	679	794	0.855	0.0000538	8148
Missense in Polyphen		261	349.89	0.74595		3556
Synonymous	-0.219	335	330	1.02	0.0000238	2519
Loss of Function	4.32	29	67.3	0.431	0.00000329	793

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000874	0.000827
Ashkenazi Jewish	0.0000997	0.0000994
East Asian	0.000414	0.000389
Finnish	0.000337	0.000278
European (Non-Finnish)	0.000264	0.000256
Middle Eastern	0.000414	0.000389
South Asian	0.000445	0.000392
Other	0.000334	0.000330

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Thick filament-associated protein located in the crossbridge region of vertebrate striated muscle a bands. In vitro it binds MHC, F-actin and native thin filaments, and modifies the activity of actin-activated myosin ATPase. It may modulate muscle contraction or may play a more structural role.
• Disease: DISEASE: Cardiomyopathy, familial hypertrophic 4 (CMH4) [MIM:115197]: 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:11499718, ECO:0000269|PubMed:11499719, ECO:0000269|PubMed:11815426, ECO:0000269|PubMed:12379228, ECO:0000269|PubMed:12628722, ECO:0000269|PubMed:12707239, ECO:0000269|PubMed:12818575, ECO:0000269|PubMed:12951062, ECO:0000269|PubMed:12974739, ECO:0000269|PubMed:14563344, ECO:0000269|PubMed:15114369, ECO:0000269|PubMed:15519027, ECO:0000269|PubMed:15563892, ECO:0000269|PubMed:16004897, ECO:0000269|PubMed:16199542, ECO:0000269|PubMed:18403758, ECO:0000269|PubMed:18929575, ECO:0000269|PubMed:18957093, ECO:0000269|PubMed:23840593, ECO:0000269|PubMed:28265379, ECO:0000269|PubMed:7744002, ECO:0000269|PubMed:9048664, ECO:0000269|PubMed:9541104, ECO:0000269|PubMed:9541115, ECO:0000269|PubMed:9562578}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cardiomyopathy, dilated 1MM (CMD1MM) [MIM:615396]: 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:20215591}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=MYBPC3 mutations may be involved in restrictive cardiomyopathy (RCM), a rare non-ischemic myocardial disease. RCM is characterized by restrictive ventricular-filling physiology in the presence of normal or reduced diastolic and/or systolic volumes (of 1 or both ventricles), biatrial enlargement, and normal ventricular wall thickness. {ECO:0000269|PubMed:26163040}.; DISEASE: Left ventricular non-compaction 10 (LVNC10) [MIM:615396]: 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. LVNC10 is an autosomal dominant condition. {ECO:0000269|PubMed:21551322}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Dilated cardiomyopathy (DCM) - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human);Striated Muscle Contraction;Striated Muscle Contraction;Muscle contraction (Consensus)

Recessive Scores

• pRec: 0.214

Intolerance Scores

• loftool: 0.498
• rvis_EVS: -0.53
• rvis_percentile_EVS: 20.54

Haploinsufficiency Scores

• pHI: 0.492
• hipred: N
• hipred_score: 0.492
• ghis: 0.510

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• gene_indispensability_pred: E
• gene_indispensability_score: 0.918

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Mybpc3
• Phenotype: homeostasis/metabolism 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: mybpc3
• Affected structure: atrium
• Phenotype tag: abnormal
• Phenotype quality: increased size

Gene ontology

• Biological process: heart morphogenesis;muscle contraction;regulation of striated muscle contraction;cell adhesion;muscle filament sliding;skeletal muscle thin filament assembly;skeletal muscle myosin thick filament assembly;positive regulation of ATPase activity;regulation of muscle filament sliding;sarcomere organization;cardiac muscle fiber development;cardiac myofibril assembly;cardiac muscle tissue morphogenesis;ventricular cardiac muscle tissue morphogenesis;cardiac muscle contraction;striated muscle myosin thick filament assembly
• Cellular component: cytosol;striated muscle myosin thick filament;striated muscle thin filament;C zone;sarcomere;Z disc;M band;A band;cardiac myofibril
• Molecular function: ATPase activator activity;protein binding;structural constituent of muscle;myosin binding;titin binding;myosin heavy chain binding;identical protein binding;metal ion binding;actin filament binding;muscle alpha-actinin binding