TPM1

tropomyosin 1, the group of Tropomyosins

Basic information

Region (hg38): 15:63042620-63071915

Previous symbols: [ "C15orf13", "CMH3" ]

Links

ENSG00000140416 ∙ NCBI:7168 ∙ OMIM:191010 ∙ HGNC:12010 ∙ Uniprot:P09493 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypertrophic cardiomyopathy 3 (Strong), mode of inheritance: AD
• familial isolated dilated cardiomyopathy (Supportive), mode of inheritance: AD
• left ventricular noncompaction (Supportive), mode of inheritance: AD
• hypertrophic cardiomyopathy 3 (Definitive), mode of inheritance: AD
• dilated cardiomyopathy 1Y (Strong), mode of inheritance: AD
• hypertrophic cardiomyopathy 3 (Strong), mode of inheritance: AD
• dilated cardiomyopathy (Moderate), mode of inheritance: AD
• arrhythmogenic right ventricular cardiomyopathy (No Known Disease Relationship), 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, dilated, 1Y; Cardiomyopathy, familial hypertrophic, 3	AD	Cardiovascular	Surveillance (eg, with echocardiography/electrocardiography), preventive measures and medical management, including ICD treatment, may be helpful to help decrease morbidity	Cardiovascular	8205619; 7898523; 11136687; 11273725; 21823217

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TPM1 gene.

• not provided (4 variants)
• Hypertrophic cardiomyopathy (3 variants)
• Hypertrophic cardiomyopathy 3 (2 variants)
• Hypertrophic cardiomyopathy 3;Dilated cardiomyopathy 1Y (1 variants)
• Cardiomyopathy (1 variants)
• Dilated cardiomyopathy 1Y (1 variants)
• Primary familial hypertrophic cardiomyopathy (1 variants)
• Primary dilated cardiomyopathy (1 variants)
• Cardiovascular phenotype (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TPM1 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			7	128	1	136
missense	4	32	282	12		330
nonsense			13			13
start loss			4			4
frameshift			6	2		8
inframe indel		2	3	1		6
splice donor/acceptor (+/-2bp)			4			4
splice region			26	25	2	53
non coding			34	117	51	202
Total	4	34	353	260	52

Highest pathogenic variant AF is 0.0000263

Variants in TPM1

This is a list of pathogenic ClinVar variants found in the TPM1 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-63042624-G-A		Dilated Cardiomyopathy, Dominant • Hypertrophic cardiomyopathy	Benign/Likely benign (Jun 14, 2016)
15-63042641-A-G			Benign (Mar 03, 2015)
15-63042644-G-A		Dilated cardiomyopathy 1Y • Hypertrophic cardiomyopathy 3	Conflicting classifications of pathogenicity (Feb 01, 2024)
15-63042645-G-C		Hypertrophic cardiomyopathy 3 • Dilated cardiomyopathy 1Y	Conflicting classifications of pathogenicity (Mar 23, 2018)
15-63042678-T-G			Benign (Mar 03, 2015)
15-63042705-C-G			Benign (Mar 03, 2015)
15-63042716-G-A		Dilated cardiomyopathy 1Y • Hypertrophic cardiomyopathy 3 • Hypertrophic cardiomyopathy 3;Dilated cardiomyopathy 1Y	Uncertain significance (Aug 03, 2021)
15-63042724-C-T		Hypertrophic cardiomyopathy 3 • Dilated cardiomyopathy 1Y • Hypertrophic cardiomyopathy 3;Dilated cardiomyopathy 1Y	Uncertain significance (Jul 28, 2021)
15-63042736-G-C		Hypertrophic cardiomyopathy 3 • Dilated cardiomyopathy 1Y	Uncertain significance (Jan 13, 2018)
15-63042743-CCGCGCTCGCACTCCCGCTCCTCCGCCCGACCG-C			Uncertain significance (Feb 02, 2021)
15-63042757-C-T			Benign (Mar 03, 2015)
15-63042782-C-T		Hypertrophic cardiomyopathy • Dilated Cardiomyopathy, Dominant	Uncertain significance (Jun 14, 2016)
15-63042783-G-T		Dilated cardiomyopathy 1Y • Hypertrophic cardiomyopathy 3	Uncertain significance (Jan 12, 2018)
15-63042789-C-T		not specified	Likely benign (Mar 23, 2017)
15-63042815-C-G		Cardiomyopathy	Uncertain significance (Sep 14, 2021)
15-63042816-T-C			Benign (Mar 03, 2015)
15-63042817-C-A		Cardiomyopathy • Hypertrophic cardiomyopathy	Uncertain significance (Nov 02, 2023)
15-63042818-G-A		Cardiomyopathy	Uncertain significance (Dec 13, 2022)
15-63042820-C-T		Cardiomyopathy	Uncertain significance (Nov 17, 2021)
15-63042823-C-A		Cardiomyopathy • Dilated cardiomyopathy 1Y;Hypertrophic cardiomyopathy 3	Uncertain significance (Oct 09, 2023)
15-63042823-C-T		Cardiomyopathy	Uncertain significance (Nov 01, 2021)
15-63042825-C-T		Cardiovascular phenotype	Uncertain significance (Jan 03, 2024)
15-63042830-A-G		Cardiovascular phenotype • Hypertrophic cardiomyopathy 3;Dilated cardiomyopathy 1Y • Hypertrophic cardiomyopathy	Uncertain significance (Apr 10, 2023)
15-63042830-AT-A		not specified	Uncertain significance (Nov 21, 2008)
15-63042831-T-C		Hypertrophic cardiomyopathy • Dilated cardiomyopathy 1Y;Hypertrophic cardiomyopathy 3	Uncertain significance (Dec 18, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TPM1	protein_coding	protein_coding	ENST00000358278	9	29284

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00102	0.989	125733	0	15	125748	0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.87	53	153	0.347	0.00000865	1877
Missense in Polyphen		17	72.738	0.23372		874
Synonymous	-1.24	69	57.1	1.21	0.00000324	486
Loss of Function	2.25	8	18.4	0.434	9.57e-7	234

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000119	0.000119
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000704	0.0000703
Middle Eastern	0.00	0.00
South Asian	0.0000980	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Binds to actin filaments in muscle and non-muscle cells (PubMed:23170982). Plays a central role, in association with the troponin complex, in the calcium dependent regulation of vertebrate striated muscle contraction (PubMed:23170982). Smooth muscle contraction is regulated by interaction with caldesmon. In non-muscle cells is implicated in stabilizing cytoskeleton actin filaments.
• Disease: DISEASE: Cardiomyopathy, familial hypertrophic 3 (CMH3) [MIM:115196]: 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:12974739, ECO:0000269|PubMed:23170982, ECO:0000269|PubMed:7898523, ECO:0000269|PubMed:8205619, ECO:0000269|PubMed:8523464, ECO:0000269|PubMed:9822100}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cardiomyopathy, dilated 1Y (CMD1Y) [MIM:611878]: 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:11273725}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Left ventricular non-compaction 9 (LVNC9) [MIM:611878]: 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. LVNC9 is an autosomal dominant condition. {ECO:0000269|PubMed:21551322}. 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);MicroRNAs in cancer - Homo sapiens (human);Disopyramide Action Pathway;Procainamide (Antiarrhythmic) Action Pathway;Phenytoin (Antiarrhythmic) Action Pathway;Fosphenytoin (Antiarrhythmic) Action Pathway;Bopindolol Action Pathway;Timolol Action Pathway;Carteolol Action Pathway;Bevantolol Action Pathway;Practolol Action Pathway;Dobutamine Action Pathway;Isoprenaline Action Pathway;Arbutamine Action Pathway;Amiodarone Action Pathway;Levobunolol Action Pathway;Metipranolol Action Pathway;Mexiletine Action Pathway;Lidocaine (Antiarrhythmic) Action Pathway;Quinidine Action Pathway;Sotalol Action Pathway;Epinephrine Action Pathway;Betaxolol Action Pathway;Atenolol Action Pathway;Alprenolol Action Pathway;Acebutolol Action Pathway;Muscle/Heart Contraction;Diltiazem Action Pathway;Propranolol Action Pathway;Pindolol Action Pathway;Penbutolol Action Pathway;Oxprenolol Action Pathway;Metoprolol Action Pathway;Esmolol Action Pathway;Bisoprolol Action Pathway;Bupranolol Action Pathway;Nebivolol Action Pathway;Amlodipine Action Pathway;Verapamil Action Pathway;Nitrendipine Action Pathway;Nisoldipine Action Pathway;Nimodipine Action Pathway;Ibutilide Action Pathway;Tocainide Action Pathway;Flecainide Action Pathway;Isradipine Action Pathway;Nifedipine Action Pathway;Felodipine Action Pathway;Nadolol Action Pathway;Carvedilol Action Pathway;Labetalol Action Pathway;miR-targeted genes in epithelium - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;miR-targeted genes in squamous cell - TarBase;Vitamin D Receptor Pathway;Striated Muscle Contraction;Smooth Muscle Contraction;Striated Muscle Contraction;Muscle contraction (Consensus)

Recessive Scores

• pRec: 0.466

Intolerance Scores

• loftool: 0.0446
• rvis_EVS: -0.43
• rvis_percentile_EVS: 25.15

Haploinsufficiency Scores

• pHI: 0.882
• hipred: Y
• hipred_score: 0.739
• ghis: 0.556

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.982

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tpm1
• Phenotype: growth/size/body region phenotype; embryo phenotype; 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)

Gene ontology

• Biological process: in utero embryonic development;positive regulation of heart rate by epinephrine;muscle contraction;regulation of muscle contraction;cytoskeleton organization;actin filament organization;regulation of heart contraction;regulation of cell shape;muscle filament sliding;negative regulation of cell migration;ruffle organization;positive regulation of ATPase activity;cellular response to reactive oxygen species;wound healing;sarcomere organization;positive regulation of cell adhesion;positive regulation of stress fiber assembly;ventricular cardiac muscle tissue morphogenesis;cardiac muscle contraction;negative regulation of vascular smooth muscle cell proliferation;negative regulation of vascular associated smooth muscle cell migration
• Cellular component: stress fiber;cytosol;cytoskeleton;muscle thin filament tropomyosin;actin filament;actin cytoskeleton;sarcomere;bleb;ruffle membrane
• Molecular function: actin binding;structural constituent of cytoskeleton;protein binding;cytoskeletal protein binding;structural constituent of muscle;identical protein binding;protein homodimerization activity;protein heterodimerization activity;actin filament binding