Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000214597 | SCV000271273 | likely pathogenic | Primary dilated cardiomyopathy | 2017-04-26 | criteria provided, single submitter | clinical testing | The p.Tyr3414fs variant in TTN has not been previously reported in individuals w ith cardiomyopathy or in large population studies, though the ability of these s tudies to accurately detect deletions may be limited. This variant is predicted to cause a frameshift, which alters the protein?s amino acid sequence beginning at position 3414 and leads to a premature termination codon 7 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 are located in the exons encoding for the A-band (Herman 2012, Pugh 2 014) or are located in an exon that is highly expressed in the heart (Roberts 20 15). The p.Tyr3414fs variant is located in the I-band in the highly expressed ex on 44. In summary, although additional studies are required to fully establish i ts clinical significance, the p.Tyr3414fs variant is likely pathogenic. |