Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000666276 | SCV000790539 | likely pathogenic | GNE myopathy | 2017-03-28 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001214257 | SCV001385931 | pathogenic | GNE myopathy; Sialuria | 2022-10-05 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Pro58 amino acid residue in GNE. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 21708040, 27829678, 28717665). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. ClinVar contains an entry for this variant (Variation ID: 551266). This missense change has been observed in individuals with autosomal recessive GNE-related myopathy (PMID: 22507750, 24005727, 24027297). 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 leucine, which is neutral and non-polar, at codon 58 of the GNE protein (p.Pro58Leu). |
| Revvity Omics, |
RCV003140061 | SCV003828625 | likely pathogenic | not provided | 2022-06-29 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000666276 | SCV004020797 | pathogenic | GNE myopathy | 2023-06-30 | criteria provided, single submitter | clinical testing | Variant summary: GNE c.173C>T (p.Pro58Leu) results in a non-conservative amino acid change located in the UDP-N-acetylglucosamine 2-epimerase domain (IPR003331) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251478 control chromosomes (gnomAD v2.1, Exomes dataset). c.173C>T has been reported in the literature in multiple compound heterozygous individuals affected with Inclusion Body Myopathy 2 (e.g., Mori-Yoshimura_2012, Cho_2014, Zhao_2015, Murtazina_2022). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 24027297, 22507750, 36360228, 25986339). Four submitters have reported clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic (n = 1) or likely pathogenic (n = 3). Based on the evidence outlined above, the variant was classified as pathogenic. |
| Baylor Genetics | RCV000666276 | SCV004191643 | pathogenic | GNE myopathy | 2023-06-08 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV000666276 | SCV002075665 | likely pathogenic | GNE myopathy | 2021-04-20 | no assertion criteria provided | clinical testing |