Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Cavalleri Lab, |
RCV001030997 | SCV001160783 | likely pathogenic | PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome | 2019-12-11 | criteria provided, single submitter | research | ACMG evidence PS2, PM2,PP2, PP3 |
Invitae | RCV001030997 | SCV003309343 | likely pathogenic | PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome | 2022-08-16 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 812174). This missense change has been observed in individual(s) with clinical features of PURA-related conditions (PMID: 32238909). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 260 of the PURA protein (p.Pro260Arg). |