Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000594042 | SCV000706458 | uncertain significance | not provided | 2018-08-28 | criteria provided, single submitter | clinical testing | |
| Counsyl | RCV000006402 | SCV000791822 | uncertain significance | GNE myopathy | 2017-05-24 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001383000 | SCV001581999 | pathogenic | GNE myopathy; Sialuria | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 256 of the GNE protein (p.Asp256Asn). This variant is present in population databases (rs121908630, gnomAD 0.02%). This missense change has been observed in individual(s) with GNE-related myopathy (PMID: 11528398). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is also known as D225N. ClinVar contains an entry for this variant (Variation ID: 6031). 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. For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000006402 | SCV002511603 | likely pathogenic | GNE myopathy | 2022-04-05 | criteria provided, single submitter | clinical testing | Variant summary: GNE c.766G>A (p.Asp256Asn) results in a conservative amino acid change located in the UDP-N-acetylglucosamine 2-epimerase domain of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 251392 control chromosomes. c.766G>A has been reported in the literature in four individuals affected with Inclusion Body Myopathy 2 from a single family, in the compound heterozygous state (Eisenberg_2001). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Two submitters classified the variant as VUS while one classified as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| OMIM | RCV000006402 | SCV000026585 | pathogenic | GNE myopathy | 2001-09-01 | no assertion criteria provided | literature only |