Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000643924 | SCV000765611 | likely pathogenic | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2018-04-20 | criteria provided, single submitter | clinical testing | This variant is an out-of-frame deletion of the genomic region spanning exons 346-362 (c.96076_107488del) of the TTN gene. This sequence change results in a premature translational stop signal in the TTN gene (p.Ile32026Profs*14). While this is not anticipated to result in nonsense mediated decay, it is expected to create a truncated TTN protein. This variant has not been reported in the literature in individuals with TTN-related disease. This variant disrupts the A-band and the M-band of the TTN gene. While this particular variant has not been reported in the literature, truncating variants in the A-band of TTN are significantly overrepresented in individuals affected with dilated cardiomyopathy (PMID: 25589632) and truncating variants in the M-band of TTN have been previously reported in individuals affected with autosomal recessive forms of myopathy and muscular dystrophy (PMID: 18948003, 23975875, 24395473). Copy number variants in these regions have not been previously reported in the literature. 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. |