ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.63370C>T (p.Gln21124Ter)

gnomAD frequency: 0.00001  dbSNP: rs1341948399
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002045099 SCV002296277 likely pathogenic Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2024-05-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln21124*) 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 0.007%). This premature translational stop signal has been observed in individual(s) with early onset atrial fibrillation (PMID: 30535219). ClinVar contains an entry for this variant (Variation ID: 1502137). This variant is located in the A band of TTN (PMID: 25589632). Truncating variants in this region are significantly overrepresented in patients affected with dilated cardiomyopathy (PMID: 25589632). Truncating variants in this region have also been reported in individuals affected with autosomal recessive centronuclear myopathy (PMID: 23975875). 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 RCV004721003 SCV005327565 likely pathogenic not provided 2023-04-06 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Located in the A-band region of TTN in which the majority of loss of function variants have been associated with autosomal dominant titinopathies (Herman et al., 2012); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 30535219, 22335739, 34495297)
Cardiogenetics and Myogenetics Molecular and Cellular Functional Unit, Aphp Sorbonne University-Hopital Pitie Salpetriere RCV004764981 SCV005374922 likely pathogenic Dilated cardiomyopathy 1G 2024-01-06 no assertion criteria provided clinical testing

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