ACTC1

actin alpha cardiac muscle 1, the group of Actins

Basic information

Region (hg38): 15:34790229-34795549

Previous symbols: [ "ACTC" ]

Links

ENSG00000159251 ∙ NCBI:70 ∙ OMIM:102540 ∙ HGNC:143 ∙ Uniprot:P68032 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypertrophic cardiomyopathy 11 (Strong), mode of inheritance: AD
• hypertrophic cardiomyopathy 11 (Strong), mode of inheritance: AD
• familial isolated dilated cardiomyopathy (Supportive), mode of inheritance: AD
• hypertrophic cardiomyopathy 11 (Definitive), mode of inheritance: AD
• hypertrophic cardiomyopathy 11 (Strong), mode of inheritance: AD
• atrial septal defect 5 (Strong), mode of inheritance: AD
• dilated cardiomyopathy 1R (Strong), mode of inheritance: AD
• hypertrophic cardiomyopathy (Definitive), mode of inheritance: AD
• dilated cardiomyopathy (Moderate), mode of inheritance: AD
• arrhythmogenic right ventricular cardiomyopathy (No Known Disease Relationship), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiomyopathy, dilated, 1R; Cardiomyopathy, familial hypertrophic 11; Atrial septal defect 5	AD	Cardiovascular	Surveillance (including with electrocardiogram and echocardiogram), preventive measures, and medical management of cardiomyopathies may be helpful to help decrease morbidity and mortality	Cardiovascular	9563954; 10330430; 10966831; 6267253; 17611253; 18467357; 18506004; 17947298; 20301486; 20301725; 21239446
Different ACTC1-related disorders have been associated with pediatric or adult-onset disease, but surveillance beginning in the pediatric period may be beneficial

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ACTC1 gene.

• not provided (156 variants)
• Cardiomyopathy (152 variants)
• Cardiovascular phenotype (106 variants)
• not specified (96 variants)
• Hypertrophic cardiomyopathy 11;Dilated cardiomyopathy 1R;Atrial septal defect 5 (85 variants)
• Dilated cardiomyopathy 1R;Atrial septal defect 5;Hypertrophic cardiomyopathy 11 (66 variants)
• Atrial septal defect 5;Hypertrophic cardiomyopathy 11;Dilated cardiomyopathy 1R (65 variants)
• Atrial septal defect 5;Dilated cardiomyopathy 1R;Hypertrophic cardiomyopathy 11 (44 variants)
• Dilated cardiomyopathy 1R;Hypertrophic cardiomyopathy 11;Atrial septal defect 5 (35 variants)
• Hypertrophic cardiomyopathy 11;Atrial septal defect 5;Dilated cardiomyopathy 1R (33 variants)
• Dilated cardiomyopathy 1R (30 variants)
• Hypertrophic cardiomyopathy 11 (29 variants)
• Hypertrophic cardiomyopathy (19 variants)
• Left ventricular noncompaction cardiomyopathy (12 variants)
• Dilated Cardiomyopathy, Dominant (11 variants)
• Atrial septal defect (11 variants)
• Familial restrictive cardiomyopathy (11 variants)
• ACTC1-related condition (7 variants)
• Primary familial hypertrophic cardiomyopathy (7 variants)
• Primary dilated cardiomyopathy (5 variants)
• Atrial septal defect 5 (4 variants)
• Inborn genetic diseases (3 variants)
• Dilated cardiomyopathy 1A (2 variants)
• Left ventricular noncompaction 4 (1 variants)
• See cases (1 variants)
• Left ventricular noncompaction 1;Dilated cardiomyopathy 1R;Atrial septal defect 5;Hypertrophic cardiomyopathy 11 (1 variants)
• Primary dilated cardiomyopathy;Left ventricular noncompaction (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ACTC1 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			2	144	2	148
missense	2	10	195			207
nonsense			5			5
start loss			2			2
frameshift	1	1	10			12
inframe indel		1	5			6
splice donor/acceptor (+/-2bp)			4			4
splice region			10	15	1	26
non coding			17	60	25	102
Total	3	12	240	204	27

Highest pathogenic variant AF is 0.0000263

Variants in ACTC1

This is a list of pathogenic ClinVar variants found in the ACTC1 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-34790275-T-A		Dilated cardiomyopathy 1R • Hypertrophic cardiomyopathy 11	Benign/Likely benign (Jan 12, 2018)
15-34790296-C-T			Benign (Mar 03, 2015)
15-34790372-C-T		Hypertrophic cardiomyopathy 11 • Dilated cardiomyopathy 1R	Uncertain significance (Jan 13, 2018)
15-34790373-G-A		Dilated cardiomyopathy 1R • Hypertrophic cardiomyopathy 11 • Dilated cardiomyopathy 1R;Hypertrophic cardiomyopathy 11;Atrial septal defect 5	Uncertain significance (Sep 07, 2021)
15-34790377-T-A		Hypertrophic cardiomyopathy 11 • Dilated cardiomyopathy 1R	Uncertain significance (Jan 12, 2018)
15-34790390-G-A		Hypertrophic cardiomyopathy 11 • Dilated cardiomyopathy 1R	Benign/Likely benign (Jan 13, 2018)
15-34790392-A-T		Dilated cardiomyopathy 1R • Hypertrophic cardiomyopathy 11	Uncertain significance (Jan 13, 2018)
15-34790396-G-A			Likely benign (Jan 24, 2018)
15-34790407-G-A		Hypertrophic cardiomyopathy	Uncertain significance (Jul 19, 2023)
15-34790407-G-C		not specified • Cardiomyopathy • Hypertrophic cardiomyopathy	Conflicting classifications of pathogenicity (Nov 20, 2023)
15-34790409-A-G		not specified	Uncertain significance (Dec 17, 2010)
15-34790411-C-A		Cardiomyopathy	Uncertain significance (Dec 18, 2019)
15-34790411-C-T		Cardiomyopathy	Uncertain significance (Dec 20, 2021)
15-34790413-T-A		Atrial septal defect 5;Hypertrophic cardiomyopathy 11;Dilated cardiomyopathy 1R	Uncertain significance (Apr 17, 2023)
15-34790415-G-A		Hypertrophic cardiomyopathy 11;Dilated cardiomyopathy 1R;Atrial septal defect 5 • not specified • Cardiovascular phenotype • Hypertrophic cardiomyopathy	Likely benign (Feb 05, 2024)
15-34790417-A-C		Hypertrophic cardiomyopathy 11;Atrial septal defect 5;Dilated cardiomyopathy 1R	Uncertain significance (Jul 26, 2021)
15-34790418-G-A		Cardiomyopathy • Atrial septal defect 5;Dilated cardiomyopathy 1R;Hypertrophic cardiomyopathy 11 • Hypertrophic cardiomyopathy	Likely benign (Jun 28, 2023)
15-34790422-T-C		Primary familial hypertrophic cardiomyopathy	Uncertain significance (Mar 16, 2017)
15-34790425-C-T		Arthrogryposis	Pathogenic (Jul 20, 2023)
15-34790426-G-A		Cardiovascular phenotype	Uncertain significance (Feb 08, 2023)
15-34790427-G-A		Atrial septal defect 5;Hypertrophic cardiomyopathy 11;Dilated cardiomyopathy 1R	Likely benign (Oct 26, 2021)
15-34790434-A-G		Cardiovascular phenotype • Cardiomyopathy • Atrial septal defect 5;Hypertrophic cardiomyopathy 11;Dilated cardiomyopathy 1R • Hypertrophic cardiomyopathy	Uncertain significance (Nov 22, 2023)
15-34790435-T-C		Cardiovascular phenotype	Uncertain significance (Apr 20, 2021)
15-34790437-G-C		Atrial septal defect 5;Dilated cardiomyopathy 1R;Hypertrophic cardiomyopathy 11	Uncertain significance (Sep 29, 2023)
15-34790438-A-G		Cardiovascular phenotype	Uncertain significance (Mar 14, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ACTC1	protein_coding	protein_coding	ENST00000290378	6	8044

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.737	0.263	125741	0	7	125748	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.52	40	235	0.170	0.0000144	2483
Missense in Polyphen		17	102.59	0.1657		1002
Synonymous	0.0654	89	89.8	0.991	0.00000550	751
Loss of Function	2.85	2	13.1	0.152	5.61e-7	161

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000878	0.0000878
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000355	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
• Disease: DISEASE: Cardiomyopathy, dilated 1R (CMD1R) [MIM:613424]: 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:9563954}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cardiomyopathy, familial hypertrophic 11 (CMH11) [MIM:612098]: 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:10330430, ECO:0000269|PubMed:10966831, ECO:0000269|PubMed:14729850, ECO:0000269|PubMed:18403758}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Atrial septal defect 5 (ASD5) [MIM:612794]: A congenital heart malformation characterized by incomplete closure of the wall between the atria resulting in blood flow from the left to the right atria. {ECO:0000269|PubMed:17947298}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cardiac muscle contraction - Homo sapiens (human);Dilated cardiomyopathy (DCM) - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);Cardiac Progenitor Differentiation;Myometrial Relaxation and Contraction Pathways;Striated Muscle Contraction (Consensus)

Recessive Scores

• pRec: 0.907

Intolerance Scores

• loftool: 0.106
• rvis_EVS: -0.21
• rvis_percentile_EVS: 38.28

Haploinsufficiency Scores

• pHI: 0.768
• hipred: Y
• hipred_score: 0.860
• ghis: 0.540

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.862

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Actc1
• 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); normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: actc1a
• Affected structure: myocardium
• Phenotype tag: abnormal
• Phenotype quality: decreased length

Gene ontology

• Biological process: positive regulation of gene expression;actin filament-based movement;muscle filament sliding;skeletal muscle thin filament assembly;actomyosin structure organization;actin-myosin filament sliding;negative regulation of apoptotic process;response to ethanol;cardiac myofibril assembly;cardiac muscle tissue morphogenesis;heart contraction;cardiac muscle contraction;mesenchyme migration
• Cellular component: extracellular space;cytoplasm;cytosol;actin filament;focal adhesion;membrane;sarcomere;lamellipodium;filopodium;I band;actomyosin, actin portion;cell body;extracellular exosome;blood microparticle;glutamatergic synapse
• Molecular function: ATP binding;ATPase activity;myosin binding