TCAP

Chr 17ADAR

titin-cap

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

The protein binds to titin Z1-Z2 domains in cardiac and skeletal muscle sarcomeres and serves as a substrate for titin kinase, functions critical for sarcomere assembly. Mutations cause autosomal recessive limb-girdle muscular dystrophy type 2G and autosomal dominant hypertrophic cardiomyopathy through a predicted gain-of-function mechanism.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
MultiplemechanismAD/ARLOEUF 0.952 OMIM phenotypes
Clinical SummaryTCAP
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Gene-Disease Validity (ClinGen)
hypertrophic cardiomyopathy · ADDisputed

Disputed — evidence questions this relationship

3 total gene-disease associations curated

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.95LOEUF
pLI 0.189
Z-score 1.67
OE 0.30 (0.120.95)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.09Z-score
OE missense 0.98 (0.831.15)
102 obs / 104.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.30 (0.120.95)
00.351.4
Missense OE0.98 (0.831.15)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 2 / 6.6Missense obs/exp: 102 / 104.5Syn Z: -0.18
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedTCAP-related hypertrophic cardiomyopathyOTHERAD
limitedTCAP-related dilated cardiomyopathyOTHERAD
DN
0.6357th %ile
GOF
0.7029th %ile
LOF
0.4135th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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