ClinVar

Description

The c.2373dupG pathogenic mutation, located in coding exon 24 of the MYBPC3 gene, results from a duplication of G at nucleotide position 2373, causing a translational frameshift with a predicted alternate stop codon (p.W792Vfs*41). This mutation has been identified in multiple unrelated individuals with hypertrophic cardiomyopathy (HCM), reported to co-segregate with disease in several families, and is published as a Dutch founder mutation (Niimura et al. N Engl J Med. 1998;338(18):1248-57 (reported as InsG791); Alders et al. Eur Heart J. 2003;24(20):1848-53; Christiaans et al. Neth Heart J. 2010;18(5):248-54 (reported as 2373_2374insG)). In the homozygous state, this mutation has been reported in a patient with neonatal lethal cardiomyopathy (Wessels MW et al. Eur. J. Hum. Genet., 2015 Jul;23:922-8). In addition, multiple functional studies have reported this mutation to result in loss of function (Moolman et al. Circulation. 2000;101(12):1396-402; van Dijk et al. Circulation. 2009;119(11):1473-83; Marston S et al. J Muscle Res Cell Motil. 2012;33(1):75-80; Wijnker PJ et al. J. Mol. Cell. Cardiol., 2016 Aug;97:82-92 (reported as 2373_2374insG)). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.