TCAP

titin-cap

Basic information

Region (hg38): 17:39665349-39666554

Previous symbols: [ "LGMD2G" ]

Links

ENSG00000173991 ∙ NCBI:8557 ∙ OMIM:604488 ∙ HGNC:11610 ∙ Uniprot:O15273 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypertrophic cardiomyopathy 25 (Limited), mode of inheritance: AD
• familial isolated dilated cardiomyopathy (Supportive), mode of inheritance: AD
• autosomal recessive limb-girdle muscular dystrophy type 2G (Supportive), mode of inheritance: AR
• hypertrophic cardiomyopathy 25 (Moderate), mode of inheritance: AD
• autosomal recessive limb-girdle muscular dystrophy type 2G (Strong), mode of inheritance: AR
• hypertrophic cardiomyopathy 25 (Strong), mode of inheritance: AD
• autosomal recessive limb-girdle muscular dystrophy type 2G (Strong), mode of inheritance: AR
• hypertrophic cardiomyopathy (Disputed Evidence), mode of inheritance: AD
• autosomal recessive limb-girdle muscular dystrophy (Definitive), mode of inheritance: AR
• dilated cardiomyopathy (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiomyopathy, dilated, 1N; Cardiomyopathy, familial hypertrophic 25; Muscular dystrophy, limb-girdle, autosomal recessive 7	AD/AR	Cardiovascular	Surveillance (eg, with echocardiography/electrocardiography) and preventive management may ameliorate/prevent severe sequelae	Cardiovascular; Musculoskeletal	9245996; 10655062; 12507422; 15582318; 16352453; 16650785; 16490376; 19412328; 18408010; 22029105; 21530252
The reported onset of heart failure has been in the adult period (including in young adults), but surveillance and early treatment may be indicated prior to adulthood; A variant has been described in an individual with intestinal pseudo-obstruction, but it is not clear if early (genetic) diagnosis would be beneficial

ClinVar

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

• Hypertrophic cardiomyopathy 25;Primary familial hypertrophic cardiomyopathy (6 variants)
• Primary familial hypertrophic cardiomyopathy;Hypertrophic cardiomyopathy 25 (5 variants)
• not provided (2 variants)
• Cardiovascular phenotype (2 variants)
• Hypertrophic cardiomyopathy 25;Autosomal recessive limb-girdle muscular dystrophy type 2G (1 variants)
• Autosomal recessive limb-girdle muscular dystrophy type 2G (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TCAP 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			3	56	2	61
missense			138	2	1	141
nonsense	3	6	2			11
start loss		1				1
frameshift	6	4	10			20
inframe indel			7			7
splice donor/acceptor (+/-2bp)	2	2				4
splice region	1	1	3	3		8
non coding			10	12	3	25
Total	11	13	170	70	6

Highest pathogenic variant AF is 0.0000131

Variants in TCAP

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

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

Position	Type	Phenotype	Significance	ClinVar
17-39665360-A-G		Primary familial hypertrophic cardiomyopathy	Likely pathogenic (Aug 07, 2018)
17-39665370-CAG-C		Abnormality of the musculature	Likely pathogenic (Jul 10, 2021)
17-39665373-A-G		Primary familial hypertrophic cardiomyopathy;Hypertrophic cardiomyopathy 25	Uncertain significance (May 05, 2023)
17-39665375-C-A		not specified • Primary familial hypertrophic cardiomyopathy;Hypertrophic cardiomyopathy 25	Uncertain significance (Nov 11, 2023)
17-39665378-A-G		Cardiovascular phenotype	Uncertain significance (Jul 21, 2023)
17-39665381-T-A		Hypertrophic cardiomyopathy 25;Primary familial hypertrophic cardiomyopathy	Uncertain significance (Feb 05, 2019)
17-39665381-T-C		Primary familial hypertrophic cardiomyopathy;Hypertrophic cardiomyopathy 25	Uncertain significance (Mar 25, 2022)
17-39665382-G-T		Primary familial hypertrophic cardiomyopathy;Hypertrophic cardiomyopathy 25	Uncertain significance (Aug 15, 2022)
17-39665383-C-T		Primary familial hypertrophic cardiomyopathy;Hypertrophic cardiomyopathy 25 • Cardiovascular phenotype • TCAP-related disorder	Likely benign (Oct 30, 2023)
17-39665382-G-GCGAGGTGT		Primary familial hypertrophic cardiomyopathy;Hypertrophic cardiomyopathy 25	Pathogenic (Jan 24, 2024)
17-39665384-G-T		Cardiovascular phenotype	Pathogenic (Jan 09, 2024)
17-39665383-C-CGAGGTGT		Autosomal recessive limb-girdle muscular dystrophy type 2G	Likely pathogenic (Aug 06, 2013)
17-39665391-C-A		Autosomal recessive limb-girdle muscular dystrophy type 2G	Likely pathogenic (Nov 04, 2013)
17-39665391-C-T		not specified • Cardiovascular phenotype • Hypertrophic cardiomyopathy 25;Primary familial hypertrophic cardiomyopathy • Cardiomyopathy • Autosomal recessive limb-girdle muscular dystrophy type 2G • Hypertrophic cardiomyopathy 25	Conflicting classifications of pathogenicity (Jan 13, 2024)
17-39665391-CG-C		Primary familial hypertrophic cardiomyopathy;Hypertrophic cardiomyopathy 25	Pathogenic (Sep 09, 2022)
17-39665391-CGGA-C		not specified • Hypertrophic cardiomyopathy 1 • Cardiovascular phenotype • Hypertrophic cardiomyopathy 25 • Primary familial hypertrophic cardiomyopathy;Hypertrophic cardiomyopathy 25 • Cardiomyopathy • Long QT syndrome	Conflicting classifications of pathogenicity (Jan 31, 2024)
17-39665391-C-CG		Autosomal recessive limb-girdle muscular dystrophy type 2G • Abnormality of the musculature • Hypertrophic cardiomyopathy 25;Primary familial hypertrophic cardiomyopathy	Pathogenic/Likely pathogenic (Jul 10, 2021)
17-39665392-G-A		Hypertrophic cardiomyopathy 25;Primary familial hypertrophic cardiomyopathy • Cardiovascular phenotype	Likely benign (Jul 06, 2022)
17-39665392-G-C		Cardiovascular phenotype • Hypertrophic cardiomyopathy 25;Primary familial hypertrophic cardiomyopathy	Likely benign (Jan 13, 2024)
17-39665392-G-T		Hypertrophic cardiomyopathy 25;Primary familial hypertrophic cardiomyopathy	Likely benign (Jan 22, 2021)
17-39665391-C-CGGAGGAGAACTGTGA		Hypertrophic cardiomyopathy 25;Primary familial hypertrophic cardiomyopathy • Cardiovascular phenotype	Uncertain significance (May 09, 2023)
17-39665393-G-C		Primary familial hypertrophic cardiomyopathy;Hypertrophic cardiomyopathy 25	Uncertain significance (Oct 28, 2022)
17-39665395-G-A		Hypertrophic cardiomyopathy 25;Primary familial hypertrophic cardiomyopathy	Likely benign (Mar 12, 2022)
17-39665396-G-A		Hypertrophic cardiomyopathy 25;Primary familial hypertrophic cardiomyopathy • Hypertrophic cardiomyopathy 25;Autosomal recessive limb-girdle muscular dystrophy type 2G	Uncertain significance (Nov 30, 2023)
17-39665400-A-ACTGTGAG		Primary familial hypertrophic cardiomyopathy;Hypertrophic cardiomyopathy 25	Pathogenic/Likely pathogenic (Nov 24, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TCAP	protein_coding	protein_coding	ENST00000309889	2	2369

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.189	0.766	125617	0	37	125654	0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0856	102	104	0.976	0.00000664	1054
Missense in Polyphen		40	48.055	0.83237		486
Synonymous	-0.182	45	43.5	1.04	0.00000246	354
Loss of Function	1.67	2	6.63	0.302	2.86e-7	71

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000623	0.0000616
Ashkenazi Jewish	0.00	0.00
East Asian	0.00120	0.00120
Finnish	0.00	0.00
European (Non-Finnish)	0.0000719	0.0000616
Middle Eastern	0.00120	0.00120
South Asian	0.000163	0.000163
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Muscle assembly regulating factor. Mediates the antiparallel assembly of titin (TTN) molecules at the sarcomeric Z-disk.
• Disease: DISEASE: Limb-girdle muscular dystrophy 2G (LGMD2G) [MIM:601954]: An autosomal recessive degenerative myopathy characterized by proximal and distal muscle weakness and atrophy in the limbs, dystrophic changes on muscle biopsy, and absence of telethonin. Cardiac muscle is involved in a subset of patients. {ECO:0000269|PubMed:10655062}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Striated Muscle Contraction;Striated Muscle Contraction;Muscle contraction (Consensus)

Recessive Scores

• pRec: 0.273

Intolerance Scores

• loftool: 0.340
• rvis_EVS: 0.46
• rvis_percentile_EVS: 78.28

Haploinsufficiency Scores

• pHI: 0.117
• hipred: N
• hipred_score: 0.248
• ghis: 0.526

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.664

Gene Damage Prediction

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

Mouse Genome Informatics

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

Zebrafish Information Network

• Gene name: tcap
• Affected structure: skeletal muscle cell
• Phenotype tag: abnormal
• Phenotype quality: increased variability of size

Gene ontology

• Biological process: somitogenesis;skeletal muscle contraction;cardiac muscle hypertrophy;adult heart development;cardiac muscle hypertrophy in response to stress;muscle filament sliding;skeletal muscle thin filament assembly;skeletal muscle myosin thick filament assembly;otic vesicle formation;response to muscle stretch;detection of muscle stretch;sarcomere organization;cardiac muscle fiber development;sarcomerogenesis;detection of mechanical stimulus;cardiac myofibril assembly;cardiac muscle tissue morphogenesis;cardiac muscle contraction;protein-containing complex assembly
• Cellular component: cytosol;Z disc;I band
• Molecular function: protein binding;structural constituent of muscle;protein binding, bridging;titin binding;BMP binding;ion channel binding;FATZ binding;titin Z domain binding