Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000158296 | SCV000208231 | likely pathogenic | not provided | 2013-04-09 | criteria provided, single submitter | clinical testing | p.Trp191Arg (TGG>CGG): c.571 T>C in exon 5 of the MYBPC3 gene (NM_000256.3). The Trp191Arg variant in the MYBPC3 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Trp191Arg results in a non-conservative amino acid substitution of a non-polar Tryptophan with a positively charged Arginine at a position that is conserved across species. In silico analysis predicts Trp191Arg is damaging to the protein structure/function. Mutations in nearby residues (Pro186Leu, Gln208His) have been reported in association with HCM, further supporting the functional importance of this region of the protein. Furthermore, the Trp191Arg variant was not observed in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.In summary, while Trp191Arg is a good candidate for a disease-causing mutation, with the clinical and molecular information available at this time we cannot unequivocally determine the clinical significance of this variant. 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). |