Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV001811839 | SCV002047950 | likely pathogenic | not provided | 2020-10-20 | criteria provided, single submitter | clinical testing | The TTN c.11709T>A; p.Cys3903* variant, to our knowledge, is not reported in the medical literature or gene specific databases. This variant is also absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant induces an early termination codon in exon 49, which is expressed in 100% of TTN transcripts, and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay (Roberts 2015). Because truncating variants in constitutively expressed exons are significantly associated with dilated cardiomyopathy, this variant is considered to be likely pathogenic (Schafer 2017). |
| Baylor Genetics | RCV003451943 | SCV004183417 | likely pathogenic | Early-onset myopathy with fatal cardiomyopathy | 2023-09-18 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV005225507 | SCV005869378 | likely pathogenic | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2024-11-07 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Cys3903*) in the TTN gene. While this is not anticipated to result in nonsense mediated decay, it is expected to create a truncated TTN protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TTN-related conditions. ClinVar contains an entry for this variant (Variation ID: 1330741). 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. |