ClinVar Miner

Submissions for variant NM_005476.7(GNE):c.737G>A (p.Arg246Gln)

gnomAD frequency: 0.00003  dbSNP: rs121908629
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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000202425 SCV000485514 likely pathogenic GNE myopathy 2015-12-29 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000725734 SCV000701108 pathogenic not provided 2017-01-26 criteria provided, single submitter clinical testing
Invitae RCV001051696 SCV001215864 pathogenic GNE myopathy; Sialuria 2023-12-14 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 277 of the GNE protein (p.Arg277Gln). This variant is present in population databases (rs121908629, gnomAD 0.01%). This missense change has been observed in individuals with autosomal recessive distal myopathy (PMID: 24695763, 29406958, 29480215). It has also been observed to segregate with disease in related individuals. This variant is also known as p.R246Q. ClinVar contains an entry for this variant (Variation ID: 6030). 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.Arg277 amino acid residue in GNE. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15987957, 22507750, 26231298). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000725734 SCV001766481 pathogenic not provided 2023-02-13 criteria provided, single submitter clinical testing Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant does not alter protein structure/function; Also known as R246Q using alternate nomenclature; This variant is associated with the following publications: (PMID: 19917666, 24027297, 25966635, 15146476, 24695763, 11528398, 29406958, 20301439, 31589614, 24796702, 33250842, 33214394, 22231866, 34676965, 30390020)
Revvity Omics, Revvity RCV000725734 SCV002018490 likely pathogenic not provided 2020-03-11 criteria provided, single submitter clinical testing
MGZ Medical Genetics Center RCV000202425 SCV002580635 pathogenic GNE myopathy 2022-01-18 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV001051696 SCV002803000 pathogenic GNE myopathy; Sialuria 2021-12-15 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000725734 SCV002821943 pathogenic not provided 2022-11-01 criteria provided, single submitter clinical testing GNE: PM3:Very Strong, PM2, PM5, PP1, PP3
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000202425 SCV004803874 pathogenic GNE myopathy 2024-01-19 criteria provided, single submitter clinical testing Variant summary: GNE c.830G>A (p.Arg277Gln) results in a conservative amino acid change located in the UDP-N-acetylglucosamine 2-epimerase domain (IPR003331) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.8e-05 in 251416 control chromosomes (gnomAD). c.830G>A has been reported in the literature as a biallelic genotype in multiple individuals affected with Inclusion Body Myopathy 2 (e.g. Lv_2022). These data indicate that the variant is very likely to be associated with disease. The following publication has been ascertained in the context of this evaluation (PMID: 35138478). ClinVar contains an entry for this variant (Variation ID: 6030). Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM RCV000202425 SCV000026584 pathogenic GNE myopathy 2001-09-01 no assertion criteria provided literature only
Sema4, Sema4 RCV000202425 SCV000196517 pathogenic GNE myopathy 2014-11-01 no assertion criteria provided clinical testing 4 patients from two non-Jewish Persian families were homozygous for this variant
GeneReviews RCV000202425 SCV001364090 not provided GNE myopathy no assertion provided literature only
Natera, Inc. RCV000202425 SCV001458437 pathogenic GNE myopathy 2020-09-16 no assertion criteria provided clinical testing

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