Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002029078 | SCV002290782 | likely pathogenic | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2021-05-25 | criteria provided, single submitter | clinical testing | This variant is a complex rearrangement of the genomic region encompassing exons 210-331 of the TTN gene. Although the exact nature of the event is unknown, it likely involves the deletion of exons 210-218, 321-330 and part of exons 320 and 331 and possibly an inversion of exons 219-319. 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 I and A bands of TTN (PMID: 25589632). The truncation likely occurs in the A band. Truncating variants in A band 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). This variant has not been reported in the literature in individuals with TTN-related conditions. |