ClinVar Miner

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

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
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
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.
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.
Soonchunhyang University Bucheon Hospital,Soonchunhyang University Medical Center RCV000343796 SCV000267347 likely pathogenic GNE myopathy 2016-03-18 criteria provided, single submitter reference population

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.