Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000118735 | SCV000153173 | pathogenic | Tibial muscular dystrophy | 2014-01-30 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000807735 | SCV000947804 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2023-11-03 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg5266*) 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 present in population databases (rs372277017, gnomAD 0.0009%). 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: 130662). 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). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Gene |
RCV003159098 | SCV003853066 | uncertain significance | not provided | 2023-03-23 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene or region of a gene for which loss of function is not a well-established mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge in association with a TTN-related disorder; This variant is associated with the following publications: (PMID: 30535219, 25589632, 27625338, 27869827) |
Grupo de Genetica Humana, |
RCV003320566 | SCV004025901 | pathogenic | Orofacial cleft 1 | 2022-11-22 | criteria provided, single submitter | research | This variant creates an early termination codon predicted to cause neuromuscular disorder. Orofacial Cleft cases associated with this mutation have been reported. This variant could also be associated with increased apoptosis of cells in the frontonasal process, an important tissue in the development of the lip and palate |