Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002543797 | SCV001511029 | pathogenic | Ocular cystinosis; Juvenile nephropathic cystinosis; Inborn genetic diseases | 2024-01-21 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 212 of the CTNS protein (p.Ala212Val). This variant is present in population databases (rs776658046, gnomAD 0.006%). This missense change has been observed in individual(s) with cystinosis (PMID: 30957593). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1020638). 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 CTNS protein function. This variant disrupts the p.Ala212 amino acid residue in CTNS. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Natera, |
RCV001835604 | SCV002093230 | uncertain significance | Cystinosis | 2020-09-22 | no assertion criteria provided | clinical testing |