ClinVar Miner

Submissions for variant NM_005476.7(GNE):c.829C>T (p.Arg277Cys) (rs762106720)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169197 SCV000220444 likely pathogenic GNE myopathy 2014-06-22 criteria provided, single submitter literature only
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000726859 SCV000703666 pathogenic not provided 2016-12-16 criteria provided, single submitter clinical testing
Invitae RCV001041020 SCV001204614 pathogenic GNE myopathy; Sialuria 2019-08-02 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 308 of the GNE protein (p.Arg308Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs762106720, ExAC 0.006%). This variant has been observed in the homozygous state or in combination with another GNE variant in several individuals affected with distal myopathy and was observed to segregate with disease in a family (PMID: 18555875, 24695763, 22507750, 29480215, 24027297). This variant is also known as p.Arg277Cys in the literature. ClinVar contains an entry for this variant (Variation ID: 188847). 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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