Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000414386 | SCV000491748 | uncertain significance | not specified | 2016-11-17 | criteria provided, single submitter | clinical testing | A novel variant of uncertain significance has been identified in the TTN gene. The c.82196-12 C>G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed 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. This single nucleotide substitution creates a potential cryptic splice acceptor site upstream of the native splice acceptor site and in silico algorithms predict it may disrupt normal splicing of intron 277. Though this substitution occurs at a position that is not conserved across species, guanine (G) is not wild type in any species. Of note, the c.82196-12 C>G variant resides in the A-band of TTN, where the majority of truncating pathogenic variants associated with DCM have been reported; however, it is not known whether this variant disrupts splicing and, if so, the effect of disrupted splicing (Herman et al., 2012). In the absence of functional mRNA studies, the physiological consequences of the c.82196-12 C>G variant cannot be precisely determined.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign. |