Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV004582575 | SCV005063191 | likely pathogenic | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2024-01-10 | criteria provided, single submitter | clinical testing | This variant results in a copy number gain of the genomic region encompassing exon(s) 224-363 of the TTN gene. While the exact position of this variant cannot be determined from the data, sub-genic copy number gains are generally in tandem (PMID: 25640679). This variant is predicted to be out-of-frame. 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 affected with TTN-related conditions. This variant disrupts the I, A, and M bands of TTN (PMID: 25589632). Truncating variants in the 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). 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. |