Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Cardiovascular Biomedical Research Unit, |
RCV000209671 | SCV000189638 | likely pathogenic | Primary dilated cardiomyopathy | 2014-10-08 | criteria provided, single submitter | research | This TTN truncating variant (TTNtv) was identified in one individual in this cohort and is located in an exon with intermediate levels of cardiac expression. In the seven cohorts assessed, TTNtv were found in 14% of ambulant DCM, 22% end-stage or familial DCM, and 2% controls. Heterozygous nonsense, frameshift and canonical splice-disrupting variants found in constitutive and other highly utilised exons are highly likely to be pathogenic when identified in individuals with phenotypically confirmed DCM. TTNtv found incidentally in healthy individuals (excluding familial assessment of DCM relatives) are thought to have low penetrance, particularly when identified in exons that are not constitutively expressed in the heart. |
| Labcorp Genetics |
RCV001853333 | SCV002133633 | likely pathogenic | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2024-10-28 | criteria provided, single submitter | clinical testing | This sequence change affects a splice site in intron 134 of the TTN gene. It is expected to disrupt RNA splicing and likely results in a truncated or disrupted TTN protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been observed in the literature in individuals with autosomal recessive TTN-related conditions. This variant has been reported in individual(s) with dilated cardiomyopathy (PMID: 25589632); however, the role of the variant in this condition is currently unclear. ClinVar contains an entry for this variant (Variation ID: 223271). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant is located in the I band of TTN (PMID: 25589632). Truncating variants in this region have been reported in individuals affected with autosomal recessive centronuclear myopathy (PMID: 23975875, internal data). Truncating variants in this region have also been identified in individuals affected with autosomal dominant dilated cardiomyopathy and/or cardio-related conditions (PMID: 27869827, 32964742, internal data). 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. |
| Ai |
RCV002223819 | SCV002502702 | likely pathogenic | not provided | 2021-08-10 | criteria provided, single submitter | clinical testing |