Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000657525 | SCV000779261 | likely pathogenic | not provided | 2018-05-09 | criteria provided, single submitter | clinical testing | The c.58306_58307delAC variant in the TTN gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The c.58306_58307delAC variant causes a frameshift starting with codon Threonine 19436, changes this amino acid to a Glutamine residue, and creates a premature Stop codon at position 14 of the new reading frame, denoted p.Thr19436GlnfsX14. This variant is predicted to cause loss of normal protein function either through 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, c.61881_61884delGAAG is located in the A-band region of titin, where the majority of truncating pathogenic variants associated with dilated cardiomyopathy (DCM) have been reported (Herman et al., 2012). Furthermore, the c.58306_58307delAC variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.58306_58307delAC as a likely pathogenic variant. |