ClinVar Genomic variation as it relates to human health
NM_006516.4(SLC2A1):c.940G>A (p.Gly314Ser)
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_006516.4(SLC2A1):c.940G>A (p.Gly314Ser)
Variation ID: 16113 Accession: VCV000016113.43
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1p34.2 1: 42929242 (GRCh38) [ NCBI UCSC ] 1: 43394913 (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 Jun 28, 2015 Oct 20, 2024 Jan 14, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_006516.4:c.940G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_006507.2:p.Gly314Ser missense NC_000001.11:g.42929242C>T NC_000001.10:g.43394913C>T NG_008232.1:g.34935G>A LRG_1132:g.34935G>A P11166:p.Gly314Ser - Protein change
- G314S
- Other names
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- Canonical SPDI
- NC_000001.11:42929241:C:T
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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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Allele frequency
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The frequency of the allele represented by this VCV record.
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- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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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
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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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| SLC2A1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
1056 | 1097 | |
Conditions - Germline
| Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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 (1) |
no assertion criteria provided
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Jun 1, 2008 | RCV000017493.38 | |
| Pathogenic (6) |
criteria provided, multiple submitters, no conflicts
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May 1, 2023 | RCV000153967.41 | |
| Pathogenic (1) |
criteria provided, single submitter
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Jan 14, 2024 | RCV000473987.19 | |
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Apr 11, 2023 | RCV001253635.10 | |
| Pathogenic (1) |
criteria provided, single submitter
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Jul 19, 2022 | RCV002288509.9 |
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
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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
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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
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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
(Jan 03, 2014)
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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: SCV000232239.5
First in ClinVar: Jun 28, 2015 Last updated: Jul 30, 2019 |
Number of individuals with the variant: 3
Sex: mixed
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Pathogenic
(Jul 19, 2022)
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criteria provided, single submitter
Method: clinical testing
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Dystonia 9
Affected status: yes
Allele origin:
germline
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MGZ Medical Genetics Center
Accession: SCV002581027.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022
Comment:
ACMG criteria applied: PS3, PS4, PM2_SUP, PP1, PP2, PP3
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Number of individuals with the variant: 1
Sex: female
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Pathogenic
(Feb 28, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000329809.8
First in ClinVar: Dec 06, 2016 Last updated: Mar 04, 2023 |
Comment:
Published functional studies demonstrate reduced glucose uptake (Weber et al., 2008); Not observed in large population cohorts (gnomAD); In silico analysis, which includes protein predictors … (more)
Published functional studies demonstrate reduced glucose uptake (Weber et al., 2008); Not observed in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 20574033, 27781031, 26615598, 18451999, 26986070, 21791420, 20507906, 25022942, 27351150, 26536893, 27128978, 26821218, 24847886, 11076005, 30895386, 31302675, 33584489) (less)
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Pathogenic
(Jan 14, 2024)
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criteria provided, single submitter
Method: clinical testing
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GLUT1 deficiency syndrome 1, autosomal recessive
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000545828.8
First in ClinVar: Apr 17, 2017 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 314 of the SLC2A1 protein (p.Gly314Ser). … (more)
This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 314 of the SLC2A1 protein (p.Gly314Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with epilepsy, mild mental retardation, and impulsivity and/or paroxysmal exertion-induced dyskinesias (PMID: 11076005, 18451999, 26615598, 27351150). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 16113). 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) performed at Invitae indicates that this missense variant is expected to disrupt SLC2A1 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects SLC2A1 function (PMID: 18451999). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jun 13, 2018)
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criteria provided, single submitter
Method: clinical testing
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Encephalopathy due to GLUT1 deficiency
Affected status: yes
Allele origin:
germline
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV001429464.1
First in ClinVar: Aug 17, 2020 Last updated: Aug 17, 2020 |
Number of individuals with the variant: 1
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Pathogenic
(Oct 23, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
(Unknown mechanism)
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001446492.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Clinical Features:
Cerebellar ataxia (present) , Hypotonia (present) , Global developmental delay (present) , Delayed speech and language development (present)
Sex: female
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Pathogenic
(Apr 11, 2023)
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criteria provided, single submitter
Method: clinical testing
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Encephalopathy due to GLUT1 deficiency
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV004172865.1
First in ClinVar: Dec 09, 2023 Last updated: Dec 09, 2023 |
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Pathogenic
(May 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV002496865.18
First in ClinVar: Apr 11, 2022 Last updated: Oct 20, 2024 |
Comment:
SLC2A1: PM2, PM5, PS2:Moderate, PS4:Moderate, PP2, PS3:Supporting
Number of individuals with the variant: 2
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Likely pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001809509.1 First in ClinVar: Aug 27, 2021 Last updated: Aug 27, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001955691.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Pathogenic
(Jun 01, 2008)
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no assertion criteria provided
Method: literature only
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GLUT1 DEFICIENCY SYNDROME 2
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000037765.3
First in ClinVar: Apr 04, 2013 Last updated: Dec 17, 2023 |
Comment on evidence:
In 5 affected members of a family with GLUT1 deficiency syndrome-2 (GLUT1DS2; 612126), Weber et al. (2008) identified a heterozygous 1119G-A transition in the SLC2A1 … (more)
In 5 affected members of a family with GLUT1 deficiency syndrome-2 (GLUT1DS2; 612126), Weber et al. (2008) identified a heterozygous 1119G-A transition in the SLC2A1 gene, resulting in a gly314-to-ser (G314S) substitution in the eighth transmembrane segment. The phenotype was characterized by childhood-onset paroxysmal exertion-induced dyskinesia with epilepsy with absences or complex partial seizures, mild learning disabilities, and an irritable behavior with increased impulsivity in 6 affected members. Hematologic abnormalities were not observed. The mutation was also identified in 2 unaffected family members, indicating decreased penetrance. The mutation was not identified in 150 controls. In vitro functional expression studies showed that the mutation decreased glucose transport but did not affect cation permeability. (less)
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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
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Paroxysmal Exercise-induced Dyskinesias Caused by GLUT1 Deficiency Syndrome. | Mongin M | Tremor and other hyperkinetic movements (New York, N.Y.) | 2016 | PMID: 27351150 |
| CoQ(10) Deficiency Is Not a Common Finding in GLUT1 Deficiency Syndrome. | Barca E | JIMD reports | 2016 | PMID: 26615598 |
| GLUT1 mutations are a cause of paroxysmal exertion-induced dyskinesias and induce hemolytic anemia by a cation leak. | Weber YG | The Journal of clinical investigation | 2008 | PMID: 18451999 |
| Familial paroxysmal exercise-induced dyskinesia and benign epilepsy: a clinical and neurophysiological study of an uncommon disorder. | Margari L | Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology | 2000 | PMID: 11076005 |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=SLC2A1 | - | - | - | - |
Text-mined citations for rs121909739 ...
HelpRecord last updated Nov 03, 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.