Submissions for variant NM_001267550.2(TTN):c.78110G>A (p.Trp26037Ter)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002898949	SCV003237563	likely pathogenic	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2023-03-02	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Trp26037*) 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 variant has not been reported in the literature in individuals affected with TTN-related conditions. ClinVar contains an entry for this variant (Variation ID: 2031879). 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.
deCODE genetics, Amgen	RCV003485795	SCV004022131	likely pathogenic	Dilated cardiomyopathy 1G	2023-07-21	no assertion criteria provided	research	The variant NM_001267550.2:c.78110G>A (chr2:178568022) in TTN was detected in 1 heterozygote out of 58K WGS Icelanders (MAF= 0,001%). This variant has not been reported in ClinVar previously. Based on ACMG criteria (PVS1, PM2) this variant classifies as likely pathogenic.