ClinVar Miner

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

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000343796 SCV000220235 pathogenic GNE myopathy 2014-04-10 criteria provided, single submitter literature only
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
GeneReviews RCV000343796 SCV000058063 pathologic GNE myopathy 2013-03-07 no assertion criteria provided curation Converted during submission to Pathogenic.

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