Submissions for variant NM_001267550.2(TTN):c.52021C>T (p.Arg17341Ter)

gnomAD frequency: 0.00001  dbSNP: rs926741242

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000459936	SCV000543001	likely pathogenic	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2023-09-08	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg17341*) 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 present in population databases (no rsID available, gnomAD 0.001%). This premature translational stop signal has been observed in individual(s) with atrial fibrillation (PMID: 30535219). ClinVar contains an entry for this variant (Variation ID: 405082). 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.
Center for Human Genetics, University of Leuven	RCV003237347	SCV002817390	likely pathogenic	Primary dilated cardiomyopathy	2022-12-31	criteria provided, single submitter	clinical testing
Muscle and Diseases Team, Institut de Génétique et Biologie Moléculaire et Cellulaire	RCV004586715	SCV005038520	likely pathogenic	Centronuclear myopathy	2024-03-01	criteria provided, single submitter	research	PVS1+PM2