NM_006516.4(SLC2A1):c.950A>C (p.Asn317Thr) AND GLUT1 deficiency syndrome 1, autosomal recessive

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jul 14, 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:: RCV002634288.3

Allele description [Variation Report for NM_006516.4(SLC2A1):c.950A>C (p.Asn317Thr)]

NM_006516.4(SLC2A1):c.950A>C (p.Asn317Thr)

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.950A>C (p.Asn317Thr)

HGVS:

NC_000001.11:g.42929232T>G
NG_008232.1:g.34945A>C
NG_090763.1:g.748T>G
NG_090764.1:g.105T>G
NM_006516.4:c.950A>CMANE SELECT
NP_006507.2:p.Asn317Thr
NP_006507.2:p.Asn317Thr
LRG_1132t1:c.950A>C
LRG_1132:g.34945A>C
LRG_1132p1:p.Asn317Thr
NC_000001.10:g.43394903T>G
NM_006516.3:c.950A>C

Protein change:

N317T

Molecular consequence:

NM_006516.4:c.950A>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
SCV003523212	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jul 14, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 18577546, 21204808, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003523212

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jul 14, 2022)

germline

clinical testing

PubMed (3)
[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

Mild adolescent/adult onset epilepsy and paroxysmal exercise-induced dyskinesia due to GLUT1 deficiency.

Afawi Z, Suls A, Ekstein D, Kivity S, Neufeld MY, Oliver K, De Jonghe P, Korczyn AD, Berkovic SF.

Epilepsia. 2010 Dec;51(12):2466-9. doi: 10.1111/j.1528-1167.2010.02726.x. Epub 2010 Sep 30.

PubMed [citation]

PMID:: 21204808

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003523212.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change affects SLC2A1 function (PMID: 18577546). 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. This missense change has been observed in individual(s) with autosomal dominant SLC2A1-related conditions (PMID: 18577546, 21204808). 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 asparagine, which is neutral and polar, with threonine, which is neutral and polar, at codon 317 of the SLC2A1 protein (p.Asn317Thr).

#	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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