ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.55800G>A (p.Trp18600Ter)

dbSNP: rs727503598
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000152296 SCV000201160 likely pathogenic Primary dilated cardiomyopathy 2014-03-12 criteria provided, single submitter clinical testing The Trp16032X variant in TTN has not been previously reported in individuals wit h cardiomyopathy or in large population studies. This nonsense variant leads to a premature termination codon at position 16032, which is predicted to lead to a truncated or absent protein. Nonsense and other truncating variants in TTN are strongly associated with DCM and the majority occur in the A-band (Herman 2012, Pugh 2014), where this variant is located. In summary, this variant is likely to be pathogenic, though additional studies are required to fully establish its cl inical significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV005222775 SCV005863002 likely pathogenic Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2024-10-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp18600*) 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 not present in population databases (gnomAD no frequency). 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: 165964). 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.

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