ClinVar Genomic variation as it relates to human health
NM_005476.7(GNE):c.1714G>C (p.Val572Leu)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_005476.7(GNE):c.1714G>C (p.Val572Leu)
Variation ID: 6033 Accession: VCV000006033.23
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 9p13.3 9: 36219940 (GRCh38) [ NCBI UCSC ] 9: 36219937 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline May 3, 2013 Feb 28, 2024 Oct 28, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_005476.7:c.1714G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_005467.1:p.Val572Leu missense NM_001128227.3:c.1807G>C MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001121699.1:p.Val603Leu missense NM_001190383.3:c.1492G>C NP_001177312.1:p.Val498Leu missense NM_001190384.3:c.1384G>C NP_001177313.1:p.Val462Leu missense NM_001190388.2:c.1537G>C NP_001177317.2:p.Val513Leu missense NM_001374797.1:c.1561G>C NP_001361726.1:p.Val521Leu missense NM_001374798.1:c.1537G>C NP_001361727.1:p.Val513Leu missense NC_000009.12:g.36219940C>G NC_000009.11:g.36219937C>G NG_008246.1:g.62105G>C LRG_1197:g.62105G>C LRG_1197t1:c.1807G>C LRG_1197p1:p.Val603Leu LRG_1197t2:c.1714G>C LRG_1197p2:p.Val572Leu Q9Y223:p.Val572Leu - Protein change
- V572L, V603L, V498L, V462L, V513L, V521L
- Other names
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- Canonical SPDI
- NC_000009.12:36219939:C:G
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.00020 (G)
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Allele frequency
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The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00002
1000 Genomes Project 30x 0.00016
1000 Genomes Project 0.00020
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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GNE | - | - |
GRCh38 GRCh37 |
1029 | 1104 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Oct 28, 2023 | RCV000006404.18 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Feb 23, 2023 | RCV000724160.9 | |
Pathogenic (1) |
criteria provided, single submitter
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Oct 6, 2023 | RCV001217981.5 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Nov 15, 2016)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000700730.2
First in ClinVar: Jan 06, 2017 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 23
Sex: mixed
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Pathogenic
(Feb 23, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV002024866.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Dec 09, 2019)
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criteria provided, single submitter
Method: clinical testing
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GNE myopathy
Affected status: unknown
Allele origin:
unknown
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Myriad Genetics, Inc.
Accession: SCV001193923.2
First in ClinVar: Apr 06, 2020 Last updated: Jul 06, 2020 |
Comment:
NM_005476.5(GNE):c.1714G>C(V572L) is classified as pathogenic in the context of GNE myopathy. Sources cited for classification include the following: PMID 16372135, 12325084, 2473753, 17164266 and 14707127. … (more)
NM_005476.5(GNE):c.1714G>C(V572L) is classified as pathogenic in the context of GNE myopathy. Sources cited for classification include the following: PMID 16372135, 12325084, 2473753, 17164266 and 14707127. Classification of NM_005476.5(GNE):c.1714G>C(V572L) 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. (less)
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Pathogenic
(Oct 28, 2023)
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criteria provided, single submitter
Method: clinical testing
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GNE myopathy
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004199378.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Oct 06, 2023)
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criteria provided, single submitter
Method: clinical testing
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Sialuria
GNE myopathy
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001389845.5
First in ClinVar: Jul 16, 2020 Last updated: Feb 28, 2024 |
Comment:
This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 603 of the GNE protein (p.Val603Leu). … (more)
This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 603 of the GNE protein (p.Val603Leu). This variant is present in population databases (rs121908632, gnomAD 0.02%). This missense change has been observed in individuals with autosomal recessive distal myopathy with rimmed vacuoles (DMRV) (PMID: 11916006, 12177386, 12325084, 12913203, 16503389, 18383535, 25257349, 26161358, 27363342, 27829678). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 6033). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GNE protein function. Experimental studies have shown that this missense change affects GNE function (PMID: 14707127). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jan 01, 2006)
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no assertion criteria provided
Method: literature only
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NONAKA MYOPATHY
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000026587.5
First in ClinVar: Apr 04, 2013 Last updated: Jan 06, 2017 |
Comment on evidence:
For discussion of the val572-to-leu (V572L) mutation in the GNE gene that was found in compound heterozygous state in patients with Nonaka myopathy (NM; 605820) … (more)
For discussion of the val572-to-leu (V572L) mutation in the GNE gene that was found in compound heterozygous state in patients with Nonaka myopathy (NM; 605820) by Kayashima et al. (2002), see 603824.0012. In 7 of 9 unrelated Japanese patients with Nonaka myopathy, Tomimitsu et al. (2002) identified a homozygous 1765G-C transversion in exon 10 of the GNE gene, resulting in a val572-to-leu (V572L) substitution. An eighth patient was a compound heterozygote for V572L and C303V (603824.0014). Arai et al. (2002) identified the V572L mutation in patients with Nonaka myopathy from 6 consanguineous Japanese families. Haplotype analysis indicated a strong founder effect in these pedigrees. Mean age of onset was 23 years, and most cases became nonambulant within 10 years of disease onset. Tomimitsu et al. (2004) identified the V572L mutation in 15 of 22 patients with Nonaka myopathy: 9 were homozygous and 6 were compound heterozygous for V572L and another mutation in the GNE gene. Kim et al. (2006) identified the V572L mutation in 7 of 8 unrelated Korean patients with Nonaka myopathy: 4 were homozygous and 3 were compound heterozygous for V572L and another mutation in the GNE gene. (less)
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Pathogenic
(Aug 04, 2021)
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no assertion criteria provided
Method: clinical testing
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Nonaka myopathy
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002075632.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
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not provided
(-)
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no classification provided
Method: literature only
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GNE myopathy
Affected status: unknown
Allele origin:
germline
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GeneReviews
Accession: SCV000058061.4
First in ClinVar: Apr 04, 2013 Last updated: Oct 01, 2022 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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GNE Myopathy. | Adam MP | - | 2020 | PMID: 20301439 |
Progression of GNE Myopathy Based on the Patient-Reported Outcome. | Park YE | Journal of clinical neurology (Seoul, Korea) | 2019 | PMID: 31286697 |
GNE myopathy in Chinese population: hotspot and novel mutations. | Chen Y | Journal of human genetics | 2019 | PMID: 30390020 |
Missing genetic variations in GNE myopathy: rearrangement hotspots encompassing 5'UTR and founder allele. | Zhu W | Journal of human genetics | 2017 | PMID: 27829678 |
Discovery of pathogenic variants in a large Korean cohort of inherited muscular disorders. | Park HJ | Clinical genetics | 2017 | PMID: 27363342 |
Novel Mutation of the GNE Gene Presenting Atypical Mild Clinical Feature: A Korean Case Report. | Choi YA | Annals of rehabilitation medicine | 2015 | PMID: 26161358 |
Mutational spectrum and clinical features in 35 unrelated mainland Chinese patients with GNE myopathy. | Zhao J | Journal of the neurological sciences | 2015 | PMID: 25986339 |
GNE myopathy associated with congenital thrombocytopenia: a report of two siblings. | Izumi R | Neuromuscular disorders : NMD | 2014 | PMID: 25257349 |
Mutation profile of the GNE gene in Japanese patients with distal myopathy with rimmed vacuoles (GNE myopathy). | Cho A | Journal of neurology, neurosurgery, and psychiatry | 2014 | PMID: 24027297 |
Heterozygous UDP-GlcNAc 2-epimerase and N-acetylmannosamine kinase domain mutations in the GNE gene result in a less severe GNE myopathy phenotype compared to homozygous N-acetylmannosamine kinase domain mutations. | Mori-Yoshimura M | Journal of the neurological sciences | 2012 | PMID: 22507750 |
Atypical Parkinsonism in distal myopathy with rimmed vacuoles. | Ishihara T | Movement disorders : official journal of the Movement Disorder Society | 2008 | PMID: 18383535 |
A Gne knockout mouse expressing human V572L mutation develops features similar to distal myopathy with rimmed vacuoles or hereditary inclusion body myopathy. | Malicdan MC | Human molecular genetics | 2007 | PMID: 17164266 |
Distal myopathy with rimmed vacuoles in a case of opercular syndrome. | Toriumi Y | Brain & development | 2006 | PMID: 16503389 |
Mutation analysis of the GNE gene in Korean patients with distal myopathy with rimmed vacuoles. | Kim BJ | Journal of human genetics | 2006 | PMID: 16372135 |
Distal myopathy with rimmed vacuoles (DMRV): new GNE mutations and splice variant. | Tomimitsu H | Neurology | 2004 | PMID: 15136692 |
Reduction of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase activity and sialylation in distal myopathy with rimmed vacuoles. | Noguchi S | The Journal of biological chemistry | 2004 | PMID: 14707127 |
GNE mutations causing distal myopathy with rimmed vacuoles with inflammation. | Yabe I | Neurology | 2003 | PMID: 12913203 |
A novel mutation in the GNE gene and a linkage disequilibrium in Japanese pedigrees. | Arai A | Annals of neurology | 2002 | PMID: 12325084 |
Distal myopathy with rimmed vacuoles: novel mutations in the GNE gene. | Tomimitsu H | Neurology | 2002 | PMID: 12177386 |
Nonaka myopathy is caused by mutations in the UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase gene (GNE). | Kayashima T | Journal of human genetics | 2002 | PMID: 11916006 |
Resolution and solution behavior of crosslinked myelin basic protein. | Caamaño CA | Biochemistry international | 1989 | PMID: 2473753 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=GNE | - | - | - | - |
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Text-mined citations for rs121908632 ...
HelpRecord last updated Mar 17, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.