NM_006516.4(SLC2A1):c.1198C>T (p.Arg400Cys) AND GLUT1 deficiency syndrome 1, autosomal recessive

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 22, 2023
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:: RCV000463311.11

Allele description [Variation Report for NM_006516.4(SLC2A1):c.1198C>T (p.Arg400Cys)]

NM_006516.4(SLC2A1):c.1198C>T (p.Arg400Cys)

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.1198C>T (p.Arg400Cys)

Other names:

p.R400C:CGT>TGT

HGVS:

NC_000001.11:g.42927685G>A
NG_008232.1:g.36492C>T
NM_006516.4:c.1198C>TMANE SELECT
NP_006507.2:p.Arg400Cys
LRG_1132:g.36492C>T
NC_000001.10:g.43393356G>A
NM_006516.2:c.1198C>T

Protein change:

R400C

Links:

dbSNP: rs796053263

NCBI 1000 Genomes Browser:

rs796053263

Molecular consequence:

NM_006516.4:c.1198C>T - 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
SCV000545832	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 22, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 22704013, 26193382, 28018440, 21555602, 22976442, 25487684, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000545832

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 22, 2023)

germline

clinical testing

PubMed (7)
[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

Allelic variations of glut-1 deficiency syndrome: the chinese experience.

Liu Y, Bao X, Wang D, Fu N, Zhang X, Cao G, Song F, Wang S, Zhang Y, Qin J, Yang H, Engelstad K, De Vivo DC, Wu X.

Pediatr Neurol. 2012 Jul;47(1):30-4. doi: 10.1016/j.pediatrneurol.2012.04.010.

PubMed [citation]

PMID:: 22704013

From splitting GLUT1 deficiency syndromes to overlapping phenotypes.

Hully M, Vuillaumier-Barrot S, Le Bizec C, Boddaert N, Kaminska A, Lascelles K, de Lonlay P, Cances C, des Portes V, Roubertie A, Doummar D, LeBihannic A, Degos B, de Saint Martin A, Flori E, Pedespan JM, Goldenberg A, Vanhulle C, Bekri S, Roubergue A, Heron B, Cournelle MA, et al.

Eur J Med Genet. 2015 Sep;58(9):443-54. doi: 10.1016/j.ejmg.2015.06.007. Epub 2015 Jul 17.

PubMed [citation]

PMID:: 26193382

See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000545832.9

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 400 of the SLC2A1 protein (p.Arg400Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with GLUT1-deficiency syndrome (PMID: 22704013, 26193382, 28018440). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 207212). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (Invitae) indicates that this missense variant is expected to disrupt SLC2A1 function with a positive predictive value of 95%. This variant disrupts the p.Arg400 amino acid residue in SLC2A1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 21555602, 22976442, 25487684). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#	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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