ClinVar Miner

Submissions for variant NM_005476.7(GNE):c.737G>A (p.Arg246Gln) (rs121908629)

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Total submissions: 6
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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
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000725734 SCV000701108 pathogenic not provided 2017-01-26 criteria provided, single submitter clinical testing
Invitae RCV001051696 SCV001215864 pathogenic GNE myopathy; Sialuria 2019-12-03 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 277 of the GNE protein (p.Arg277Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with hereditary inclusion-body myopathy in at least one family (PMID: 24695763) and has also been observed in individuals with hereditary inclusion-body myopathy (PMID: 29480215, 24695763). This variant is also known as p.R246Q in the literature. ClinVar contains an entry for this variant (Variation ID: 6030). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but 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. This variant disrupts the p.Arg277 amino acid residue in GNE. Another variant that disrupts this residue has been observed in individuals with GNE-related conditions (PMID: 15987957, 26231298, 15987957, 22507750), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been 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 pathogenic GNE myopathy 2020-04-07 no assertion criteria provided literature only

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