Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000726859 | SCV000703666 | pathogenic | not provided | 2016-12-16 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001041020 | SCV001204614 | pathogenic | GNE myopathy; Sialuria | 2023-10-27 | 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 308 of the GNE protein (p.Arg308Cys). This variant is present in population databases (rs762106720, gnomAD 0.01%). This missense change has been observed in individuals with distal myopathy (PMID: 18555875, 22507750, 24027297, 24695763, 29480215). It has also been observed to segregate with disease in related individuals. This variant is also known as p.Arg277Cys. ClinVar contains an entry for this variant (Variation ID: 188847). 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. This variant disrupts the p.Arg308 amino acid residue in GNE. Other variant(s) that disrupt this residue have been observed in individuals with GNE-related conditions (PMID: 24027297), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |
Myriad Genetics, |
RCV000169197 | SCV002060388 | likely pathogenic | GNE myopathy | 2021-11-03 | criteria provided, single submitter | clinical testing | NM_001128227.2(GNE):c.922C>T(R308C) is a missense variant classified as likely pathogenic in the context of GNE myopathy. R308C has been observed in cases with relevant disease (PMID: 24027297, 24695763, 22231866, 27858732, 29997562, 29480215). Functional assessments of this variant are not available in the literature. R308C has been observed in population frequency databases (gnomAD: EAS 0.01%). NM_001128227.2(GNE):c.922C>T(R308C) is a missense variant that has been observed more frequently in cases with the relevant disease than in healthy populations. Please note: this variant was assessed in the context of healthy population screening. |
Revvity Omics, |
RCV000726859 | SCV003824653 | pathogenic | not provided | 2022-06-25 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000169197 | SCV004038920 | pathogenic | GNE myopathy | 2023-08-10 | criteria provided, single submitter | clinical testing | Variant summary: GNE c.922C>T (p.Arg308Cys) 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 allele was found at a frequency of 2e-05 in 251480 control chromosomes. c.922C>T has been reported in the literature as biallelic genotypes in multiple individuals affected with GNE/Inclusion Body Myopathy 2 (example, Mori-Yoshimura_2012, Cerino_2015). 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: 27858732, 24695763, 22507750, 22231866). Five submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Baylor Genetics | RCV000169197 | SCV004199385 | pathogenic | GNE myopathy | 2023-09-28 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV000169197 | SCV002075658 | pathogenic | GNE myopathy | 2020-07-17 | no assertion criteria provided | clinical testing |