Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000668839 | SCV000793507 | likely pathogenic | GNE myopathy | 2017-08-17 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV000668839 | SCV004191666 | pathogenic | GNE myopathy | 2023-02-05 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV003767968 | SCV004569726 | likely pathogenic | GNE myopathy; Sialuria | 2023-05-24 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 208 of the GNE protein (p.Arg208Cys). This variant is present in population databases (rs539332585, gnomAD 0.01%). This missense change has been observed in individuals with autosomal recessive distal myopathy (PMID: 12473753, 24027297, 25986339). This variant is also known as R177C. ClinVar contains an entry for this variant (Variation ID: 553400). 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 GNE protein function. Experimental studies have shown that this missense change affects GNE function (PMID: 14707127). 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. |