Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000482417 | SCV000571502 | likely pathogenic | not provided | 2016-09-02 | criteria provided, single submitter | clinical testing | The P260L variant in the PURA gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The P260L variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The P260L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret P260L as a likely pathogenic variant |
Invitae | RCV001342491 | SCV001536426 | uncertain significance | PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome | 2020-04-24 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with PURA-related conditions. ClinVar contains an entry for this variant (Variation ID: 422115). This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with leucine at codon 260 of the PURA protein (p.Pro260Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. |