Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000578542 | SCV000681019 | pathogenic | not provided | 2017-08-04 | criteria provided, single submitter | clinical testing | The Q69X variant in the PURA gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is predicted to cause loss of normal protein function through protein truncation. The Q69X variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret Q69X as a pathogenic variant. |
| Invitae | RCV000803739 | SCV000943624 | pathogenic | PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome | 2018-11-09 | criteria provided, single submitter | clinical testing | This sequence change results in a premature translational stop signal in the PURA gene (p.Gln69*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 294 amino acids of the PURA protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PURA-related disease. ClinVar contains an entry for this variant (Variation ID: 489041). This variant disrupts the C-terminus of the PURA protein. Other variant(s) that disrupt this region (p.Gln186*, p.Tyr261*) have been determined to be pathogenic (PMID: 25439098). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic. |