Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001008174 | SCV001167940 | likely pathogenic | not provided | 2018-05-01 | criteria provided, single submitter | clinical testing | The c.49815delC likely pathogenic variant in the TTN gene has not been published as pathogenic or benign to our knowledge. c.49815delC causes a shift in reading frame starting at codon Methionine 16606, changing it to a Tryptophan, and creating a premature stop codon at position 3 of the new reading frame, denoted p.Met16606TrpfsX3. 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 (Herman et al., 2012). However, c.49815delC 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). Moreover, the c.49815delC variant has not been observed in large population cohorts (Lek et al., 2016). |