Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000220480 | SCV000271282 | likely pathogenic | Primary dilated cardiomyopathy | 2016-01-11 | criteria provided, single submitter | clinical testing | The p.Glu24264X 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 24264 which is predicted to lead to a truncated or absent protein. Nonsense and other truncating variants in TTN are strongly associated with DCM if they impact the exons encoding for the A-band ( Herman 2012, Pugh 2014) or are located in an exon that is highly expressed in th e heart (Roberts 2015). This variant is located the highly expressed exon 275 of the A-band. In summary, although additional studies are required to fully estab lish its clinical significance, the p.Glu24264X variant is likely pathogenic. |
Gene |
RCV000480047 | SCV000570090 | likely pathogenic | not provided | 2016-04-22 | criteria provided, single submitter | clinical testing | The E25191X variant in the TTN gene has not been reported as a pathogenic variant or as a benign variant to our knowledge. E25191X is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Other truncating TTN variants have been reported in approximately 3% of control alleles (Herman et al., 2012). However, E25191X is located in the A-band region of titin, where the majority of truncating pathogenic variants associated with DCM have been reported (Herman et al., 2012). Furthermore, the E25191X variant was not observed in approximately 6,100 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The E25191X variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded. |