Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000579144 | SCV000680852 | uncertain significance | not provided | 2016-06-09 | criteria provided, single submitter | clinical testing | A novel variant of uncertain significance has been identified in the TTN gene. The Q3898X variant has not been reported previously as a pathogenic variant or as a benign variant, to our knowledge. This variant was not observed with any significant frequency in approximately 5,900 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Q3898X is predicted to cause loss of normal protein function either due to production of an abnormal, prematurely truncated protein, or by absence of protein product due to nonsense mediated mRNA decay. However, Q3898X is not 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, other truncating TTN variants have been reported in approximately 3% of control alleles (Herman et al., 2012).Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign. |