Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001338247 | SCV001531899 | uncertain significance | PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome | 2022-12-20 | 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. This variant disrupts the p.Arg199 amino acid residue in PURA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 25439098). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PURA protein function. ClinVar contains an entry for this variant (Variation ID: 1035387). This variant has not been reported in the literature in individuals affected with PURA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 199 of the PURA protein (p.Arg199Cys). |
| Gene |
RCV003317481 | SCV004021451 | uncertain significance | not provided | 2023-01-18 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |