ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.96838C>T (p.Gln32280Ter)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002635273 SCV002969009 likely pathogenic Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2022-10-26 criteria provided, single submitter clinical testing This variant is also known as c.89134C>T (p.Gln29712*). This premature translational stop signal has been observed in individual(s) with dilated cardiomyopathy (PMID: 30847666; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln32280*) 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 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 RCV003225240 SCV003921608 likely pathogenic not provided 2022-10-20 criteria provided, single submitter clinical testing Reported in association with dilated cardiomyopathy (van Lint et al., 2019); Not observed at significant frequency in large population cohorts (gnomAD); 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); 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; This variant is associated with the following publications: (PMID: 22335739, 30847666)

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