Key result
DES c.832C>T variant linked to arrhythmogenic cardiomyopathy featuring ventricular arrhythmias and ~45% mean LVEF.
Why the study?
The ACMG/AMP pathogenicity classification of the DES c.832C>T (p.R278W) variant remains disputed among commercial genetic laboratories despite reports in DCM and HCM cohorts.
Case Report (n=5)
The DES c.832C>T (p.R278W) variant is associated with an arrhythmogenic cardiomyopathy characterized by late gadolinium enhancement, ventricular arrhythmias, and inflammatory myocardial changes, supported by abnormal desmin aggregation in vitro.
Warrants cascade screening and longitudinal cardiac follow-up in families; extends genotype-phenotype relationships for DES variants.
Pathogenic variants in DES, encoding the intermediate filament protein desmin, are linked to a spectrum of cardiomyopathies, including dilated (DCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC). The DES c.832C>T (p.R278W) variant has been reported in DCM and hypertrophic cardiomyopathy (HCM) cohorts, though its ACMG/AMP pathogenicity classification remains disputed among commercial genetic laboratories (ClinVar Variation ID: 201703). We describe five individuals carrying this variant, their associated cardiac phenotypes, and complementary cellular studies assessing the biological effect of this variant on DES structure.
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Melly et al. (2026) conducted a case report in Cardiomyopathy (n=5). DES c.832C>T (p.R278W) variant was evaluated on Cardiac phenotypes and biological effect on DES structure. The DES c.832C>T (p.R278W) variant was evaluated in five individuals to characterize its associated inflammatory and arrhythmogenic cardiac phenotypes and structural effects.
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