The causal link between missense mutations in the human cardiac alpha-actin gene ('ACTC') and cardiac muscle disease phenotypes including hypertrophic and dilated cardiomyopathy has been well established. However, the molecular mechanisms by which different mutations lead to distinct cardiomyopathies are unknown. Here, six ACTC variants with single amino acid substitutions linked to dilated and hypertrophic cardiomyopathy were expressed and purified employing the baculovirus/'Sf9' expression system and DNase-I affinity chromatography. Using the DNase-I inhibition assay, circular dichroism and the pyrene fluorescence polymerization assay, the folding efficiency, thermal stability of the actin variant monomers, as well as the ability to form normal filaments were investigated. The M305L and E361G-ACTC proteins appear to be only moderately affected with IC50 and monomer melting temperature values similar to wildtype ACTC. The R312H, Y166C, A230V, and A331P variants however, show more severe defects in folding and decreased thermal stability which translated to significant deficiencies in polymerization and altered filament morphology ' in vitro'. The results of this thesis extend previous findings and provide support for the hypothesis that impaired filament formation and/or self-association of partially folded monomers could be one of the cellular pathological effects of ACTC substitutions.