Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002032058 | SCV002309832 | likely pathogenic | not provided | 2023-06-24 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1524903). 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PNPT1 protein function. This missense change has been observed in individual(s) with clinical features of PNPT1-related conditions (PMID: 33587123). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 113 of the PNPT1 protein (p.Pro113Ser). |
| Athena Diagnostics | RCV002032058 | SCV002817203 | uncertain significance | not provided | 2019-10-31 | criteria provided, single submitter | clinical testing | This observation is not an independent occurrence and has been identified in the same individual by RCIGM, the other laboratory participating in the GEMINI study. |