Submissions for variant NM_001267550.2(TTN):c.86640C>A (p.Tyr28880Ter)

dbSNP: rs794729298

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001866265	SCV002315806	likely pathogenic	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2021-10-19	criteria provided, single submitter	clinical testing	This variant is also known as c.78936C>A, p.Tyr26312*. This premature translational stop signal has been observed in individual(s) with clinical features of TTN-related conditions (PMID: 30847666, 31737537). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Tyr28880*) 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.
Clinical Genetics, Academic Medical Center	RCV001700868	SCV001918361	pathogenic	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001700868	SCV001927495	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001700868	SCV001953574	likely pathogenic	not provided		no assertion criteria provided	clinical testing