Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001008919 | SCV001168725 | likely pathogenic | not provided | 2018-06-29 | criteria provided, single submitter | clinical testing | Although the c.39542_39543delTG likely pathogenic variant in the TTN gene has not been reported to our knowledge, this variant causes a shift in reading frame starting at codon leucine 13181, changing it to a glutamine, and creating a premature stop codon at position 32 of the new reading frame, denoted p.Leu13181GlnfsX32. 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. Other truncating TTN variants have been reported in approximately 3% of control alleles, and the majority of truncating pathogenic variants associated with DCM have been reported in the A-band (Herman et al., 2012). However, the c.39542_39543delTG variant is located in one of the constitutive exons in the I-band region, and recent studies suggest that truncating variants affecting constitutive exons throughout the TTN gene are also significantly associated with DCM (Deo, 2016; Schafer et al., 2017). Lastly, the c.39542_39543delTG variant has not been observed in large population cohorts (Lek et al., 2016). |