TNNI3 – Arrhythmogenic Right Ventricular Cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an autosomal dominant‐inherited myocardial disorder characterized by ventricular arrhythmias and fibro‐fatty replacement of the right ventricle. In a cohort of 43 advanced cardiomyopathy index patients (10 ARVC), one proband carried a heterozygous TNNI3 missense variant c.380A>G (p.Asp127Gly) (PMID:29253866). In a separate series of 137 ARVC patients meeting 2010 Task Force Criteria and negative for desmosomal mutations, one individual (1/137, 0.7%) was found to harbor the same TNNI3 c.380A>G variant (PMID:29709087). Both reports noted that these rare sarcomeric variants are predicted damaging but lacked informative familial cosegregation.

No ARVC‐specific functional assays of TNNI3 variants have been reported; existing experimental work focuses on troponin I in hypertrophic or dilated cardiomyopathy contexts. Given the limited number of probands (2 unrelated) and absence of segregation or mechanistic data in ARVC, the pathogenic role of TNNI3 in ARVC remains unconfirmed. Key Take-home: Current evidence for TNNI3 in ARVC is limited, and identified variants should be interpreted with caution in clinical genetic testing.

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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