Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000692464 | SCV000820289 | likely pathogenic | Spastic paraplegia | 2018-06-28 | criteria provided, single submitter | clinical testing | This sequence change results in a premature translational stop signal in the GJC2 gene (p.Val30Argfs*10). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 410 amino acids of the GJC2 protein. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Other truncations (p.Arg125*, p.Tyr232*, p.Arg240*) that lie downstream of this variant have been reported in individuals affected with Pelizaeus-Merzbacher-like disease disease (PMID: 20513814, 18094336, 15192806). This variant has not been reported in the literature in individuals with GJC2-related disease. This variant is not present in population databases (ExAC no frequency). |