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TNNT2 – Arrhythmogenic Right Ventricular Cardiomyopathy

TNNT2 (cardiac troponin T) has been suggested as a candidate gene for arrhythmogenic right ventricular cardiomyopathy (ARVC) based on a single consanguineous pedigree in which two siblings presented with severe ARVD and asymptomatic anterior polar cataract, mapping to 14q23–24 under a putative autosomal recessive model (PMID:9409860). In a larger follow-up study screening 137 ARVC probands for sarcomeric gene variants, TNNT2 mutations were not identified among the 6 probands (4%) carrying rare sarcomeric alterations, indicating lack of replication in this cohort (PMID:29709087). Overall, genetic evidence linking TNNT2 to ARVC remains limited, with no variant-level segregation or functional data supporting pathogenicity in this disease context.

Key take-home: current data do not support routine TNNT2 testing for ARVC in clinical practice.

References

  • American journal of medical genetics • 1997 • Arrhythmogenic right ventricular dysplasia and anterior polar cataract. PMID:9409860
  • Journal of cardiovascular electrophysiology • 2018 • Identification of sarcomeric variants in probands with a clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC). PMID:29709087

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

Single family with two affected siblings under AR inheritance, no TNNT2 variant identified; no replication in cohort studies

Genetic Evidence

Limited

Minimal case-level support: locus mapping only in one pedigree; no TNNT2 mutations in 137 ARVC probands

Functional Evidence

No evidence

No functional assays directly linking TNNT2 variants to ARVC phenotypes