TCAP

Chr 17ADAR

titin-cap

Also known as: CMD1N, CMH25, LGMD2G, LGMDR7, T-cap, TELE, telethonin

NCBI Gene: 8557ENSG00000173991UniProt: O15273

Sarcomere assembly is regulated by the muscle protein titin. Titin is a giant elastic protein with kinase activity that extends half the length of a sarcomere. It serves as a scaffold to which myofibrils and other muscle related proteins are attached. This gene encodes a protein found in striated and cardiac muscle that binds to the titin Z1-Z2 domains and is a substrate of titin kinase, interactions thought to be critical to sarcomere assembly. Mutations in this gene are associated with limb-girdle muscular dystrophy type 2G. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Cardiomyopathy, hypertrophic, 25MIM #607487
AD
Muscular dystrophy, limb-girdle, autosomal recessive 7MIM #601954
AR
UniProtCardiomyopathy, familial hypertrophic, 25
398
ClinVar variants
43
Pathogenic / LP
0.19
pLI score
0
Active trials
Clinical Summary— TCAP
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.
📋
ClinVar Variants
43 Pathogenic / Likely Pathogenic· 216 VUS of 398 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.95LOEUF
pLI 0.189
Z-score 1.67
OE 0.30 (0.12–0.95)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.09Z-score
OE missense 0.98 (0.83–1.15)
102 obs / 104.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.30 (0.12–0.95)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.83–1.15)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.04
0≤1.21.6
LoF obs/exp: 2 / 6.6Missense obs/exp: 102 / 104.5Syn Z: -0.18

ClinVar Variant Classifications

398 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic19
VUS216
Likely Benign106
Benign7
Conflicting26
24
Pathogenic
19
Likely Pathogenic
216
VUS
106
Likely Benign
7
Benign
26
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
1
14
0
24
Likely Pathogenic
9
2
8
0
19
VUS
14
172
28
2
216
Likely Benign
0
3
20
83
106
Benign
0
1
4
2
7
Conflicting
—26
Total321797487398

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TCAP · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

TCAP-related hypertrophic cardiomyopathy

disputed
ADUndeterminedUncertain
Cardiac
G2P ↗

TCAP-related dilated cardiomyopathy

limited
ADUndeterminedUncertain
Cardiac
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
TITIN-CAP; TCAP
MIM #604488 · *

Cardiomyopathy, hypertrophic, 25

MIM #607487

Molecular basis of disorder known

Autosomal dominant

Muscular dystrophy, limb-girdle, autosomal recessive 7

MIM #601954

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Clinical features, imaging findings and molecular data of limb-girdle muscular dystrophies in a cohort of Chinese patients.
Lin F et al.·Orphanet J Rare Dis
2023Cohort
TCAP gene is not a common cause of cardiomyopathy in Iranian patients.
Alaei Z et al.·Eur J Med Res
2023Cohort
The clinical features and TCAP mutation spectrum in a Chinese cohort of patients with limb-girdle muscular dystrophy R7.
Lv X et al.·Hum Mol Genet
2023Cohort
Distal myopathy due to TCAP variants in four unrelated Chinese patients.
Lv X et al.·Neurogenetics
2021Cohort
Role of the teneurins, teneurin C-terminal associated peptides (TCAP) in reproduction: clinical perspectives.
Lovejoy DA et al.·Horm Mol Biol Clin Investig
2015
Tcap gene mutations in hypertrophic cardiomyopathy and dilated cardiomyopathy.
Hayashi T et al.·J Am Coll Cardiol
2004
Findings of limb-girdle muscular dystrophy R7 telethonin-related patients from a Chinese neuromuscular center.
Huang K et al.·Neurogenetics
2022Cohort
Novel TCAP mutation c.32C>A causing limb girdle muscular dystrophy 2G.
Francis A et al.·PLoS One
2014
A pilot study of muscle plasma protein changes after exercise.
Dahlqvist JR et al.·Muscle Nerve
2014
Screening of hub genes and immunocytes related to tendon injury based on bioinformatics and machine learning models.
Sun S et al.·Sci Rep
2025Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Development of tCAP(N3): Affinity Peptide-Aided, pH-Triggered Strategy for Site-Specific Native IgG Modification.
Kawakami H et al.·Chemistry
2026🔓 Open Access
AAV-based TCAP delivery rescues mitochondria dislocation in limb-girdle muscular dystrophy R7.
Lv X et al.·Brain
2025
Mutations in the TCAP gene may lead to restrictive phenotype hypertrophic cardiomyopathy with poor prognosis: case report.
Hu Y et al.·Eur Heart J Case Rep
2025🔓 Open AccessCase report
Teneurin C-Terminal Associated Peptide (TCAP)-1 Attenuates Restraint Stress-Induced Corticosterone Increases in Male Mice and Rats.
Mueller LE et al.·Pharmacol Res Perspect
2024🔓 Open Access
Tcap deficiency impedes striated muscle function and heart regeneration with elevated ROS and autophagy.
Zhao Y et al.·Biochim Biophys Acta Mol Basis Dis
2024
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools