ClinVar

Description

p.Arg1205Gln (CGG>CAG):c.3614 G>A in exon 32 of the MYBPC3 gene (NM_000256.3)The Arg1205Gln variant in the MYBPC3 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Arg1205Gln results in a non-conservative amino acid substitution of positively charged Arginine with a neutral, polar Glutamine at a position that is conserved across species. Mutations in nearby residues (Leu1200Pro, Gly1206Asp, Gly1206Val) have been reported in association with cardiomyopathy, further supporting the functional importance of this region of the protein. Furthermore, the NHLBI ESP Exome Variant Server reports Arg1205Gln was not observed in approximately 6,000 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations.In summary, Arg1205Gln in the MYBPC3 gene is a good candidate for a disease-causing mutation. Mutations in the MYBPC3 gene have been reported in 20%-30% of patients with autosomal dominant familial hypertrophic cardiomyopathy, and have been reported less frequently in patients with autosomal dominant familial dilated cardiomyopathy (Cirino A et al., 2011; Hershberger R et al., 2009). The variant is found in HCM panel(s).