Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000778884 | SCV000915286 | uncertain significance | GNE myopathy | 2017-08-22 | criteria provided, single submitter | clinical testing | TheGNE c.2096C>T (p.Ser699Leu) missense variant has been reported in a single study in which it was identified in one patient with neuromuscular disease in a compound heterozygous state along with a second missense variant (No et al. 2013). Control data are unavailable for this variant, which is reported at a frequency of 0.00505 in the Esan in Nigeria population of the 1000 Genomes Project, but this is based on one allele only and it is presumed to be rare. Based on the limited evidence, the p.Ser699Leu variant is classified as a variant of unknown significance but suspicious for pathogenicity for GNE-related myopathy. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
| Illumina Laboratory Services, |
RCV001165629 | SCV001327842 | uncertain significance | Sialuria | 2017-08-21 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
| Labcorp Genetics |
RCV001856164 | SCV002250931 | likely pathogenic | GNE myopathy; Sialuria | 2025-01-26 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 730 of the GNE protein (p.Ser730Leu). This variant is present in population databases (rs552758282, gnomAD 0.007%). This missense change has been observed in individuals with autosomal recessive GNE-related myopathy (PMID: 23437777, 33250842). This variant is also known as p.Ser699Leu. ClinVar contains an entry for this variant (Variation ID: 632044). Invitae Evidence 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 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. 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. |