ClinVar Miner

Submissions for variant NM_005476.7(GNE):c.1442G>A (p.Arg481Gln) (rs138357804)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000727190 SCV000620691 uncertain significance not provided 2017-09-06 criteria provided, single submitter clinical testing The R512Q variant in the GNE gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R512Q variant is observed in 5/8652 (0.06%) alleles from individuals of East Asian background in the ExAC dataset. The R512Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret R512Q as a variant of uncertain significance.
Invitae RCV000531870 SCV000632646 uncertain significance GNE myopathy; Sialuria 2019-07-11 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 512 of the GNE protein (p.Arg512Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs138357804, ExAC 0.06%). This variant has not been reported in the literature in individuals with GNE-related disease. ClinVar contains an entry for this variant (Variation ID: 451929). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000727190 SCV000706495 uncertain significance not provided 2018-03-23 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.