Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001008790 | SCV001168585 | likely pathogenic | not provided | 2018-09-24 | criteria provided, single submitter | clinical testing | The c.53072delA likely pathogenic variant in the TTN gene has previously been reported in three unrelated patients with DCM, who each harbored additional variants in TTN or other genes (Pugh et al., 2014). This variant causes a shift in reading frame starting at codon Histidine 17691, changing it to a Proline, and creating a premature stop codon at position 18 of the new reading frame, denoted p.His17691ProfsX18. This likely pathogenic variant is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Although other truncating TTN variants have been reported in approximately 3% of control alleles, the c.53072delA variant is located in the A band region of titin, where the majority of truncating variants associated with DCM have been reported (Herman et al., 2012). Furthermore, the c.53072delA variant has not been observed in large population cohorts (Lek et al., 2016). |
| CHEO Genetics Diagnostic Laboratory, |
RCV001798167 | SCV002042557 | likely pathogenic | Cardiomyopathy | 2020-01-21 | criteria provided, single submitter | clinical testing | |
| Laboratory for Molecular Medicine, |
RCV000040401 | SCV000064092 | likely pathogenic | Primary dilated cardiomyopathy | 2013-02-07 | no assertion criteria provided | clinical testing | The His16764fs variant in TTN has not been reported in the literature, but has b een identified by our laboratory in 3 individuals with DCM, who each carried add itional variants of unknown significance. In 1 family, the variant segregated wi th disease in 2 affected relatives (1 with AF, 1 with DCM). This variant is pred icted to cause a frameshift, which alters the protein's amino acid sequence begi nning at codon 16764 and leads to a premature stop codon 18 amino acids downstre am. This alteration is then predicted to lead to a truncated or absent protein ( loss of function). Truncating variants in the TTN gene are strongly associated w ith DCM (Herman 2012). In summary, this variant is likely to be pathogenic, thou gh additional studies are needed to establish this with certainty. |