Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000155681 | SCV000205391 | likely pathogenic | Primary dilated cardiomyopathy | 2015-03-13 | criteria provided, single submitter | clinical testing | The p.Asp21656fs variant in TTN has been previously reported in 1 adolescent wit h DCM and segregated with disease in 3 affected family members (reported as c.67 746delT, p.Pro22582fs, Herman 2012). Data from large population studies is insuf ficient to assess its frequency in the general population. This variant is predi cted to cause a frameshift, which alters the protein?s amino acid sequence begin ning at position 21656 and leads to a premature termination codon 8 amino acids downstream. This alteration is then predicted to lead to a truncated or absent p rotein. Frameshift and other truncating variants in TTN are strongly associated with DCM, particularly if they are located in the exons encoding for the A-band region of the protein (Herman 2012, Pugh 2014), where this variant is located. I n summary, although additional studies are required to fully establish its clini cal significance, the p.Asp21656fs variant is likely pathogenic. |
| Labcorp Genetics |
RCV000461414 | SCV000542626 | pathogenic | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2024-08-31 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asp24224Ilefs*8) 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 (rs727504531, gnomAD 0.006%). This premature translational stop signal has been observed in individuals with dilated cardiomyopathy (PMID: 22335739). It has also been observed to segregate with disease in related individuals. This variant is also known as c.67745delT. ClinVar contains an entry for this variant (Variation ID: 178908). 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). For these reasons, this variant has been classified as Pathogenic. |
| Provincial Medical Genetics Program of British Columbia, |
RCV002056100 | SCV002320872 | pathogenic | Dilated cardiomyopathy 1G | 2022-01-01 | criteria provided, single submitter | clinical testing | |
| University of Washington Center for Mendelian Genomics, |
RCV000155681 | SCV001434756 | uncertain significance | Primary dilated cardiomyopathy | no assertion criteria provided | research |