Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000612609 | SCV000711980 | likely pathogenic | Primary dilated cardiomyopathy | 2016-04-14 | criteria provided, single submitter | clinical testing | The p.Gly22580fs variant in TTN has not been previously reported in individuals with cardiomyopathy or in large population studies, though the ability of these studies to accurately detect indels may be limited. This variant is predicted to cause a frameshift, which alters the protein?s amino acid sequence beginning at position 22580 and leads to a premature termination codon 11 amino acids downst ream. This alteration is then predicted to lead to a truncated or absent protein . Frameshift and other truncating variants in TTN are strongly associated with D CM 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.Gly22580fs variant is located in A-band in the highly expressed exon 275. In summary, although additional studies are required to fully establish its cli nical significance, the p.Gly22580fs variant is likely pathogenic. |