NM_006516.4(SLC2A1):c.418G>C (p.Val140Leu) AND GLUT1 deficiency syndrome 1, autosomal recessive

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 8, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000648085.7

Allele description [Variation Report for NM_006516.4(SLC2A1):c.418G>C (p.Val140Leu)]

NM_006516.4(SLC2A1):c.418G>C (p.Val140Leu)

Gene:

SLC2A1:solute carrier family 2 member 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p34.2

Genomic location:

Preferred name:

NM_006516.4(SLC2A1):c.418G>C (p.Val140Leu)

HGVS:

NC_000001.11:g.42930724C>G
NG_008232.1:g.33453G>C
NM_006516.4:c.418G>CMANE SELECT
NP_006507.2:p.Val140Leu
LRG_1132:g.33453G>C
NC_000001.10:g.43396395C>G
NM_006516.2:c.418G>C

Protein change:

V140L

Links:

dbSNP: rs1057517822

NCBI 1000 Genomes Browser:

rs1057517822

Molecular consequence:

NM_006516.4:c.418G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: GLUT1 deficiency syndrome 1, autosomal recessive
Identifiers:: MedGen: C3149117

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000769895	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 8, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 18577546, 29356177, 31273778, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000769895

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 8, 2022)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Paroxysmal exercise-induced dyskinesia and epilepsy is due to mutations in SLC2A1, encoding the glucose transporter GLUT1.

Suls A, Dedeken P, Goffin K, Van Esch H, Dupont P, Cassiman D, Kempfle J, Wuttke TV, Weber Y, Lerche H, Afawi Z, Vandenberghe W, Korczyn AD, Berkovic SF, Ekstein D, Kivity S, Ryvlin P, Claes LR, Deprez L, Maljevic S, Vargas A, Van Dyck T, et al.

Brain. 2008 Jul;131(Pt 7):1831-44. doi: 10.1093/brain/awn113. Epub 2008 Jun 24.

PubMed [citation]

PMID:: 18577546
PMCID:: PMC2442425

Proline-rich transmembrane protein 2-negative paroxysmal kinesigenic dyskinesia: Clinical and genetic analyses of 163 patients.

Tian WT, Huang XJ, Mao X, Liu Q, Liu XL, Zeng S, Guo XN, Shen JY, Xu YQ, Tang HD, Yin XM, Zhang M, Tang WG, Liu XR, Tang BS, Chen SD, Cao L.

Mov Disord. 2018 Mar;33(3):459-467. doi: 10.1002/mds.27274. Epub 2018 Jan 22.

PubMed [citation]

PMID:: 29356177

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000769895.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Val140 amino acid residue in SLC2A1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 18577546, 29356177). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 140 of the SLC2A1 protein (p.Val140Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with SLC2A1-related conditions (PMID: 31273778; Invitae). ClinVar contains an entry for this variant (Variation ID: 538677). 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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