Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000155712 | SCV000205422 | likely pathogenic | Primary dilated cardiomyopathy | 2013-04-21 | criteria provided, single submitter | clinical testing | The Trp30275X variant in TTN has not been reported in individuals with cardiomyo pathy or in large population studies. This nonsense variant leads to a premature termination codon at position 30275, which is predicted to lead to a truncated or absent protein. Nonsense and other truncating variants in TTN are strongly as sociated with DCM and the majority occur in the A-band (Herman 2012, LMM unpubli shed data), where this variant is located. In summary, the predicted impact of t his variant suggests that it is likely pathogenic, but additional studies are ne eded to fully establish its clinical significance. |
Invitae | RCV000815550 | SCV000956011 | likely pathogenic | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2022-11-24 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp32843*) in the TTN gene. While this is not anticipated to result in nonsense mediated decay, it is expected to create a truncated TTN protein. 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 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). ClinVar contains an entry for this variant (Variation ID: 178936). This variant has not been reported in the literature in individuals affected with TTN-related conditions. This variant is not present in population databases (gnomAD no frequency). |