Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000216926 | SCV000271284 | likely pathogenic | Primary dilated cardiomyopathy | 2016-03-07 | criteria provided, single submitter | clinical testing | The p.Glu26245X variant in TTN has not been previously reported in individuals w ith cardiomyopathy or in large population studies. This nonsense variant leads t o a premature termination codon at position 26245, which is predicted to lead to a truncated or absent protein. Nonsense and other truncating variants in TTN ar e strongly associated with DCM if they impact the exons encoding for the A-band (Herman 2012, Pugh 2014) and/or are located in an exon that is highly expressed in the heart (Roberts 2015). The p.Glu26245X variant is located in A-band in the highly expressed exon 275. In summary, although additional studies are required to fully establish its clinical significance, the p.Glu26245X variant is likely pathogenic. |
Gene |
RCV000283799 | SCV000330780 | pathogenic | not provided | 2016-09-14 | criteria provided, single submitter | clinical testing | The E27172X variant in the TTN gene has not been reported as a pathogenic variant or as a benign variant to ourknowledge. However, this variant is predicted to cause loss of normal protein function either by protein truncation ornonsense-mediated mRNA decay. Furthermore, E27172X is located in the A-band region of TTN, where the majorityof truncating variants associated with DCM have been reported (Herman et al., 2012). Finally, E27172X was notobserved in approximately 6,200 individuals of European and African American ancestry in the NHLBI ExomeSequencing Project, indicating it is not a common benign variant in these populations.In summary, E27172X in the TTN gene is interpreted as a pathogenic variant. |