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- Comprehensive analysis of genetic variants in the MYBPC3 gene: databases, variants and structural impactPublication . Gomes, Ana Letícia Fernandes; Bruque, Carlos David; Martel, PauloHypertrophic Cardiomyopathy (HCM) is the most common inherited cardiomyopathy and genes encoding sarcomere proteins have been reported to be the primary cause of the disease. MYBPC3, encoding cardiac myosin binding protein C (MyBP-C), is the first candidate gene to study genetic cases in HCM. MyBP-C is a sarcomeric protein that binds to both actin and myosin, and regulates cardiac contractility. Due to the increasing number of variants described in MYBPC3, a better understanding of the disease-causing mechanisms and correct interpretation of the biological implications are required when determining its pathogenicity. Here, we create an extensive dataset, from the literature between 1995 and 2017, containing information about pathogenic MYBPC3 variants. A total of 106 articles containing information on MYBPC3 pathogenic variants were assembled. The next step was, curate the nomenclature, according to the Human Genome Variation Society (HGVS) and Mutalyzer 3 (https://mutalyzer.nl/). Additionally, all variants from the literature dataset were reclassified according to the American College of Medical Genetics and Genomics (ACMG) guidelines. The assembling of 603 MYBPC3 genomic variants from previous publications enables us to standardize the variants to the same terminology, reduce redundancy, and identify MYBPC3 genotype-phenotype correlations. The final analysis of our work focuses on missense variants and their possible impact on MyBP-C protein. Our findings provide strong support on pathogenicity for missense variants, through protein structure destability and influence MyBP-C protein important binding sites.