TNNT2

Chr 1AD

troponin T2, cardiac type

Also known as: CMD1D, CMH2, CMPD2, LVNC6, RCM3, TnTC, cTnT

NCBI Gene: 7139 ENSG00000118194 UniProt: P45379 OMIM: 191045

The cardiac troponin T protein is the tropomyosin-binding subunit of the troponin complex that confers calcium-sensitivity to cardiac muscle contraction. Mutations cause autosomal dominant cardiomyopathies including hypertrophic, dilated, restrictive, and left ventricular noncompaction phenotypes. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.638), and comprehensive clinical management guidelines are available through GeneReviews.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes the cardiac isoform of troponin T. The encoded protein is the tropomyosin-binding subunit of the troponin complex, which is located on the thin filament of striated muscles and regulates muscle contraction in response to alterations in intracellular calcium ion concentration. Mutations in this gene have been associated with familial hypertrophic cardiomyopathy as well as with dilated cardiomyopathy. [provided by RefSeq, May 2022]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Cardiomyopathy, dilated, 1DMIM #601494

Cardiomyopathy, familial restrictive, 3MIM #612422

Cardiomyopathy, hypertrophic, 2MIM #115195

Left ventricular noncompaction 6MIM #601494

Clinical highlights

Gene–disease validity (ClinGen)

Active trials

—

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.64

LOEUF

Mechanism· predicted

📖

GeneReview available — TNNT2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.64LOEUF

pLI 0.002

Z-score 2.92

OE 0.37 (0.22–0.64)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.19Z-score

OE missense 0.74 (0.64–0.86)

121 obs / 163.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.37 (0.22–0.64)

0≤0.351.4

Missense OE?0.74 (0.64–0.86)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 9 / 24.6Missense obs/exp: 121 / 163.9Syn Z: 0.06

Background carrier burden — how many people carry a rare variant somewhere in TNNT2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

435 rare PASS variants

Rare truncating (LoF)

1 in 790

82 rare PASS variants

Rare synonymous (reference)

1 in 150

175 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TNNT2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 140	1 in 710
South Asian	~43k	1 in 93	1 in 2,000
Remaining (unassigned)	~30k	1 in 110	1 in 690
European (Finnish)	~27k	1 in 520	≈ 1 in 13,000
Admixed American	~22k	1 in 120	1 in 740
African / African American	~21k	1 in 110	1 in 1,100
East Asian	~20k	1 in 110	1 in 4,000
Ashkenazi Jewish	~13k	1 in 610	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 110	≈ 1 in 660

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 15 of 16 coding exons well covered in gnomAD exomes; exon 4 marginal. Genomes: 15 of 16 (exon 4 below).? see exons ↓