ClinVar Miner

Submissions for variant NM_005476.7(GNE):c.527A>T (p.Asp176Val) (rs139425890)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Soonchunhyang University Bucheon Hospital,Soonchunhyang University Medical Center RCV000343796 SCV000267347 likely pathogenic GNE myopathy 2016-03-18 criteria provided, single submitter reference population
Illumina Clinical Services Laboratory,Illumina RCV000343796 SCV000480110 pathogenic GNE myopathy 2017-04-27 criteria provided, single submitter clinical testing The GNE c.527A>T (p.Asp176Val) variant is a well-described pathogenic variant (Mori-Yoshimura et al. 2014; Zhao et al. 2015). In the Japanese nationwide patient registry, which includes 121 patients with GNE-related myopathy, the p.Asp176Val variant is found in a homozygous state in one individual, in a compound heterozygous state with the common p.Val572Leu variant in 24 individuals, in a compound heterozygous state with different variants in 29 individuals, and in a heterozygous state in three individuals (Mori-Yoshimura et al. 2014). The p.Asp176Val variant is additionally reported in three other studies in which it is found in 37 patients of Chinese origin including three in a homozygous state and 34 in a compound heterozygous state, and in one Korean patient in a compound heterozygous state (Lu et al; 2011; Choi et al. 2015; Zhao et al. 2015). The p.Asp176Val variant was detected in a heterozygous state in one of 520 control individuals and is reported at a frequency of 0.00046 in the East Asian population of the Exome Aggregation Consortium. Functional studies using a p.Asp176Val transgenic mouse model found that the mouse mimicked the clinical, histopathological, and biochemical features of GNE-related myopathy, however, the p.Asp176Val variant was also reported in a homozygous state in a 71 year old asymptomatic individual (Cho et al. 2014). Although the p.Asp176Val variant has been identified at a high frequency of individuals with GNE-related myopathy, the variability in clinical presentation is suggestive of a milder phenotype and potentially reduced penetrance. Based on the collective evidence, the p.Asp176Val variant is classified as pathogenic for GNE-related myopathy. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000726858 SCV000703656 pathogenic not provided 2016-11-16 criteria provided, single submitter clinical testing
Myriad Women's Health, Inc. RCV000343796 SCV001193885 pathogenic GNE myopathy 2019-12-24 criteria provided, single submitter clinical testing NM_001128227.2(GNE):c.620A>T(D207V, aka D176V) is classified as pathogenic in the context of GNE myopathy. Sources cited for classification include the following: PMID 17704511, 14707127 and 24027297. Classification of NM_001128227.2(GNE):c.620A>T(D207V, aka D176V) is based on the following criteria: This is a well-established pathogenic variant in the literature that has been observed more frequently in patients with clinical diagnoses than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.
Invitae RCV001060883 SCV001225600 pathogenic GNE myopathy; Sialuria 2019-12-02 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with valine at codon 207 of the GNE protein (p.Asp207Val). The aspartic acid residue is highly conserved and there is a large physicochemical difference between aspartic acid and valine. This variant is present in population databases (rs139425890, ExAC 0.05%). This variant has been observed to be homozygous or in combination with another GNE variant in individuals affected with distal myopathy (PMID: 12473753, 18383535, 26161358, 14707127, 29307446, 28403181). ClinVar contains an entry for this variant (Variation ID: 41233). This variant has been reported to affect GNE protein function (PMID: 28895049, 14707127, 24474513, 20030229). For these reasons, this variant has been classified as Pathogenic.
GeneReviews RCV000343796 SCV000058063 pathogenic GNE myopathy 2020-04-07 no assertion criteria provided literature only

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