ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.15796C>T (p.Arg5266Ter)

gnomAD frequency: 0.00001  dbSNP: rs372277017
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000118735 SCV000153173 pathogenic Tibial muscular dystrophy 2014-01-30 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000807735 SCV000947804 likely pathogenic Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2024-07-21 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 premature translational stop signal has been observed in individual(s) with autosomal recessive TTN-related conditions (PMID: 36781956). This variant is also known as p.Arg4022*. 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 reported in individuals affected with autosomal recessive centronuclear myopathy (PMID: 23975875, Invitae 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, Invitae 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.
GeneDx 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, Facultad de Medicina - Universidad de La Sabana 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

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