Submissions for variant NM_001267550.2(TTN):c.82895_82896del (p.Thr27632fs)

dbSNP: rs796267411

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000482519	SCV000573265	likely pathogenic	not provided	2025-02-10	criteria provided, single submitter	clinical testing	Frameshift 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; Identified in patients with dilated cardiomyopathy in published literature, although detailed clinical information was not provided; also described as c.82895_82896delCA and c.75191_75192del (PMID: 27813223, 30847666); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 30847666, 27813223, 22335739, 32778822)
Labcorp Genetics (formerly Invitae), Labcorp	RCV002526672	SCV003524874	likely pathogenic	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2021-12-27	criteria provided, single submitter	clinical testing	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. ClinVar contains an entry for this variant (Variation ID: 423555). This sequence change creates a premature translational stop signal (p.Thr27632Serfs*5) 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 premature translational stop signal has been observed in individual(s) with dilated cardiomyopathy (PMID: 27813223, 30847666). This variant is also known as c.75191_75192del (p.Thr25064Serfs*5).
Clinical Genetics, Academic Medical Center	RCV000482519	SCV001920624	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000482519	SCV001963152	likely pathogenic	not provided		no assertion criteria provided	clinical testing