Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000152330 | SCV000201222 | likely pathogenic | Primary dilated cardiomyopathy | 2014-07-17 | criteria provided, single submitter | clinical testing | The Lys14841fs variant in TTN has not been reported in individuals with cardiomy opathy or in large population studies. This frameshift variant is predicted to a lter the protein?s amino acid sequence beginning at position 14841 and lead to a premature termination codon 23 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Frameshift and other truncat ing variants in TTN are strongly associated with DCM and the majority occur in e xons encoding for the A-band region of the protein (Herman 2012, Pugh 2014), whe re this variant is located. In summary, this variant is likely pathogenic, thoug h additional studies are required to fully establish its clinical significance. |
| Labcorp Genetics |
RCV001857522 | SCV002285083 | likely pathogenic | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2021-06-23 | criteria provided, single submitter | clinical testing | This variant is located in the A band of TTN (PMID: 25589632). Truncating variants in this region are significantly overrepresented in patients affected with dilated cardiomyopathy (PMID: 25589632). Truncating variants in this region have also been reported in individuals affected with autosomal recessive centronuclear myopathy (PMID: 23975875). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant has not been reported in the literature in individuals with TTN-related conditions. ClinVar contains an entry for this variant (Variation ID: 165996). This sequence change creates a premature translational stop signal (p.Lys17409Thrfs*23) in the TTN gene. While this is not anticipated to result in nonsense mediated decay, it is expected to create a truncated TTN protein. This variant is not present in population databases (ExAC no frequency). |