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In a cohort of 137 individuals meeting 2010 Task Force Criteria for arrhythmogenic right ventricular cardiomyopathy (PMID:29709087), negative for desmosomal and other common ARVC‐associated genes, screening of sarcomere genes identified rare variants in six probands, including a single TPM1 missense change. No cosegregation of TPM1 variants with disease was observed, and no functional validation specific to TPM1 in ARVC has been reported, leaving the pathogenicity uncertain. As α-tropomyosin is critical to sarcomere stability, mechanistic plausibility exists, but current data are insufficient to establish causality. Routine inclusion of TPM1 in ARVC diagnostic panels should be interpreted with caution, pending additional family segregation and in vitro or in vivo functional studies. Key take-home: TPM1 variants are occasionally detected in ARVC but their clinical interpretation is currently limited.
Gene–Disease AssociationLimitedSingle proband with TPM1 variant in ARVC ([PMID:29709087]); no segregation or functional evidence Genetic EvidenceLimitedOne rare TPM1 missense variant identified; no segregation data and variant only predicted damaging Functional EvidenceNo EvidenceNo functional assays of TPM1 variants in ARVC reported |