TNNC1 – Arrhythmogenic Right Ventricular Cardiomyopathy

Cardiac troponin C (TNNC1) encodes the calcium-binding subunit of the troponin complex essential for sarcomeric contraction. In a cohort of 43 advanced cardiomyopathy index patients, including 10 with arrhythmogenic right ventricular cardiomyopathy (ARVC), two probands were found to harbor rare TNNC1 missense variants (c.184G>A (p.Asp62Asn)) classified as likely pathogenic (PMID:29253866). No affected relatives were available to assess segregation, and subsequent screening of 137 ARVC patients did not identify additional TNNC1 variants, highlighting the rarity of these findings (PMID:29709087).

To date, there are no ARVC-specific functional or animal model studies of TNNC1 variants. The absence of family segregation and lack of mechanistic validation in ARVC contexts limit the gene–disease correlation. Consequently, TNNC1’s role in ARVC remains provisional, and routine clinical testing should interpret TNNC1 variants with caution pending further evidence.

References

• PloS one • 2017 • High proportion of genetic cases in patients with advanced cardiomyopathy including a novel homozygous Plakophilin 2-gene mutation. PMID:29253866
• Journal of cardiovascular electrophysiology • 2018 • Identification of sarcomeric variants in probands with a clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC). PMID:29709087

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