Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000616863 | SCV000712247 | likely pathogenic | Primary dilated cardiomyopathy | 2016-06-10 | criteria provided, single submitter | clinical testing | The p.Pro11756Alafs variant in TTN has not been previously reported in individua ls with cardiomyopathy or in large population studies. This variant is predicted to cause a frameshift, which alters the protein?s amino acid sequence beginning at position 11756 and leads to a premature termination codon 11 amino acids dow nstream. This alteration is then predicted to lead to a truncated or absent prot ein. Truncating variants in TTN are strongly associated with DCM if they impact the exons encoding for the A-band (Herman 2012, Pugh 2014) and/or are located in an exon that is highly expressed in the heart (Roberts 2015). The p.Pro11756Ala fs variant is located in the highly expressed exon 182 in the I band. In summary , although additional studies are required to fully establish its clinical signi ficance, the p.Pro11756Alafs variant is likely pathogenic. |