Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000152412 | SCV000201441 | uncertain significance | not specified | 2014-11-06 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Pathogenic. The p.Gly4360fs variant in TTN has not been previously reported in individuals with cardiomyopa thy or in large population studies. This variant is predicted to cause a framesh ift, which alters the protein?s amino acid sequence beginning at position 4360 a nd leads to a premature termination codon 3 amino acids downstream. This alterat ion is then predicted to lead to a truncated or absent protein. Frameshift and o ther truncating variants in TTN are strongly associated with DCM, particularly i f they are located in the exons encoding for the A-band region of the protein (H erman 2012, Pugh 2014). Variants in the I-band, where the p.Gly4360fs variant is located, occur at a greater frequency in controls than in individuals with DCM (Pugh 2014). This decreases the likelihood, but does not rule out that this vari ant has a role in disease. In summary, while the predicted impact of this varian t provides some suspicion for a pathogenic role, its clinical significance is un certain |