Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002664274 | SCV003524881 | likely pathogenic | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2022-10-01 | criteria provided, single submitter | clinical testing | 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 band of TTN (PMID: 25589632). Truncating variants in this region have been shown to be highly prevalent in the general population and unaffected individuals (PMID: 26701604, 22335739). However, truncating variants in this region have also been reported in individuals affected with autosomal recessive centronuclear myopathy (PMID: 23975875). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Disruption of this splice site has been observed in individual(s) with autosomal recessive TTN-related conditions (PMID: 27868403). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs747942388, gnomAD 0.01%). This sequence change affects an acceptor splice site in intron 49 of the TTN gene. It is expected to disrupt RNA splicing and likely results in a truncated or disrupted TTN protein. |
| Cardiogenetics and Myogenetics Molecular and Cellular Functional Unit, |
RCV004764991 | SCV005375113 | uncertain significance | Dilated cardiomyopathy 1G | 2024-01-06 | no assertion criteria provided | clinical testing |