Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003764532 | SCV004604158 | uncertain significance | GNE myopathy; Sialuria | 2023-10-03 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 607 of the GNE protein (p.Gly607Glu). This variant is present in population databases (rs121908625, gnomAD 0.003%). This missense change has been observed in individual(s) with autosomal recessive inclusion body myopathy (PMID: 11528398). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as G576E. ClinVar contains an entry for this variant (Variation ID: 6026). 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: 16503651). 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. |
| OMIM | RCV000006397 | SCV000026580 | pathogenic | GNE myopathy | 2001-09-01 | no assertion criteria provided | literature only |