Submissions for variant NM_001267550.2(TTN):c.58388del (p.Asn19463fs)

dbSNP: rs2050854171

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001222864	SCV001394986	likely pathogenic	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2019-06-17	criteria provided, single submitter	clinical testing	This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). 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. This sequence change results in a premature translational stop signal in the TTN gene (p.Asn19463Thrfs*22). While this is not anticipated to result in nonsense mediated decay, it is expected to create a truncated TTN protein.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001529609	SCV001743342	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001529609	SCV001974960	pathogenic	not provided		no assertion criteria provided	clinical testing