ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.22930C>T (p.Arg7644Ter)

gnomAD frequency: 0.00001  dbSNP: rs1340940049
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV002254955 SCV001371399 uncertain significance not provided 2020-06-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001309106 SCV001498590 likely pathogenic Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2024-02-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg7644*) 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 (no rsID available, 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: 932569). 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 RCV002254955 SCV002526338 likely pathogenic not provided 2022-06-07 criteria provided, single submitter clinical testing 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; Not located in a region of TTN in which loss of function variants are significantly associated with titinopathies; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge
Clinical Genetics Laboratory, University Hospital Schleswig-Holstein RCV002290994 SCV002583483 pathogenic Dilated cardiomyopathy 1G 2022-06-02 no assertion criteria provided clinical testing

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