Submissions for variant NM_001267550.2(TTN):c.61290T>A (p.Cys20430Ter)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003780987	SCV004569500	likely pathogenic	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2023-06-14	criteria provided, single submitter	clinical testing	This premature translational stop signal has been observed in individual(s) with dilated cardiomyopathy (PMID: 22335739). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Cys20430*) 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 also known as c.56367T>A (p.Cys18789X). 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. 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).