ClinVar Genomic variation as it relates to human health
NM_006516.4(SLC2A1):c.377G>A (p.Arg126His)
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.377G>A (p.Arg126His)
Variation ID: 16111 Accession: VCV000016111.43
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1p34.2 1: 42930765 (GRCh38) [ NCBI UCSC ] 1: 43396436 (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 Nov 23, 2014 Jun 17, 2024 Jul 13, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_006516.4:c.377G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_006507.2:p.Arg126His missense NC_000001.11:g.42930765C>T NC_000001.10:g.43396436C>T NG_008232.1:g.33412G>A LRG_1132:g.33412G>A P11166:p.Arg126His - Protein change
- R126H
- Other names
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- Canonical SPDI
- NC_000001.11:42930764: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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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 |
1038 | 1076 |
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/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Apr 11, 2023 | RCV000017491.48 | |
Pathogenic/Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Jul 13, 2023 | RCV000081432.34 | |
Pathogenic (1) |
criteria provided, single submitter
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Oct 17, 2022 | RCV001387741.14 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Jun 27, 2022 | RCV002288508.9 |
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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Likely pathogenic
(Jun 27, 2022)
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criteria provided, single submitter
Method: clinical testing
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Childhood onset GLUT1 deficiency syndrome 2
Affected status: yes
Allele origin:
germline
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MGZ Medical Genetics Center
Accession: SCV002580975.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022
Comment:
ACMG criteria applied: PS3_MOD, PS4_MOD, PM5, PM6, PM2_SUP, PP3
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Number of individuals with the variant: 1
Sex: female
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Pathogenic
(Jul 13, 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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GeneDx
Accession: SCV000491172.3
First in ClinVar: Mar 24, 2015 Last updated: Jul 22, 2023 |
Comment:
Published functional studies suggest that the R126H variant results in reduced glucose update (Brockmann et al., 2001; Jiang et al., 2010); In silico analysis supports … (more)
Published functional studies suggest that the R126H variant results in reduced glucose update (Brockmann et al., 2001; Jiang et al., 2010); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 12181017, 18387950, 21069159, 17052934, 24847886, 20574033, 15622525, 29530121, 32005694, 31175295, 34992632, 11603379, 19798636, 12325075) (less)
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Pathogenic
(Oct 17, 2022)
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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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Invitae
Accession: SCV001588450.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg126 amino acid residue in SLC2A1. Other variant(s) that disrupt this … (more)
For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg126 amino acid residue in SLC2A1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17718830, 19798636, 21546317, 26193382). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects SLC2A1 function (PMID: 11603379). 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. ClinVar contains an entry for this variant (Variation ID: 16111). This missense change has been observed in individuals with glucose transporter type 1 (GLUT1) deficiency (PMID: 11603379, 29530121). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 126 of the SLC2A1 protein (p.Arg126His). (less)
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Pathogenic
(Feb 08, 2013)
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criteria provided, single submitter
Method: clinical testing
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GLUT1 deficiency syndrome 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000194965.1
First in ClinVar: Nov 23, 2014 Last updated: Nov 23, 2014 |
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Pathogenic
(Mar 12, 2013)
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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: SCV000230328.5
First in ClinVar: Jun 28, 2015 Last updated: Jul 31, 2019 |
Number of individuals with the variant: 1
Sex: mixed
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Likely 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: SCV004173481.1
First in ClinVar: Dec 09, 2023 Last updated: Dec 09, 2023 |
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Likely pathogenic
(Jun 01, 2018)
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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: SCV000891826.24
First in ClinVar: Mar 31, 2019 Last updated: Jun 17, 2024 |
Number of individuals with the variant: 1
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Pathogenic
(Oct 01, 2001)
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no assertion criteria provided
Method: literature only
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GLUT1 DEFICIENCY SYNDROME 1
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000037763.3
First in ClinVar: Apr 04, 2013 Last updated: Dec 17, 2023 |
Comment on evidence:
In affected members of a family with GLUT1 deficiency (GLUT1DS1; 606777), Brockmann et al. (2001) identified a heterozygous arg126-to-his (R126H) missense mutation in the SLC2A1 … (more)
In affected members of a family with GLUT1 deficiency (GLUT1DS1; 606777), Brockmann et al. (2001) identified a heterozygous arg126-to-his (R126H) missense mutation in the SLC2A1 gene. (less)
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not provided
(-)
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no classification provided
Method: literature only
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Encephalopathy due to GLUT1 deficiency
Affected status: unknown
Allele origin:
germline
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GeneReviews
Accession: SCV002556352.2
First in ClinVar: Aug 08, 2022 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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[Glucose transporter 1 deficiency syndrome: features of movement disorders, diagnosis and treatment]. | Ji XN | Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics | 2018 | PMID: 29530121 |
Glucose Transporter Type 1 Deficiency Syndrome. | Adam MP | - | 2018 | PMID: 20301603 |
From splitting GLUT1 deficiency syndromes to overlapping phenotypes. | Hully M | European journal of medical genetics | 2015 | PMID: 26193382 |
Video/EEG recording of myoclonic absences in GLUT1 deficiency syndrome with a hot-spot R126C mutation in the SLC2A1 gene. | Gökben S | Epilepsy & behavior : E&B | 2011 | PMID: 21546317 |
Early-onset absence epilepsy caused by mutations in the glucose transporter GLUT1. | Suls A | Annals of neurology | 2009 | PMID: 19798636 |
GLUT1 deficiency syndrome--2007 update. | Klepper J | Developmental medicine and child neurology | 2007 | PMID: 17718830 |
Autosomal dominant glut-1 deficiency syndrome and familial epilepsy. | Brockmann K | Annals of neurology | 2001 | PMID: 11603379 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=SLC2A1 | - | - | - | - |
Text-mined citations for rs80359816 ...
HelpRecord last updated Jun 23, 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.