NM_006516.4(SLC2A1):c.884C>T (p.Thr295Met) AND GLUT1 deficiency syndrome 1, autosomal recessive

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 8, 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:: RCV001380032.8

Allele description [Variation Report for NM_006516.4(SLC2A1):c.884C>T (p.Thr295Met)]

NM_006516.4(SLC2A1):c.884C>T (p.Thr295Met)

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.884C>T (p.Thr295Met)

Other names:

p.T295M:ACG>ATG

HGVS:

NC_000001.11:g.42929298G>A
NG_008232.1:g.34879C>T
NM_006516.4:c.884C>TMANE SELECT
NP_006507.2:p.Thr295Met
LRG_1132t1:c.884C>T
LRG_1132:g.34879C>T
NC_000001.10:g.43394969G>A
NM_006516.2:c.884C>T
NM_006516.3:c.884C>T
P11166:p.Thr295Met

Protein change:

T295M

Links:

UniProtKB: P11166#VAR_054763; dbSNP: rs80359823

NCBI 1000 Genomes Browser:

rs80359823

Molecular consequence:

NM_006516.4:c.884C>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
SCV001577959	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 8, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 17052934, 18614966, 15622525, 16949238, 20630673, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001577959

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 8, 2023)

germline

clinical testing

PubMed (6)
[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

Disease-associated Glut1 single amino acid substitute mutations S66F, R126C, and T295M constitute Glut1-deficiency states in vitro.

Wong HY, Law PY, Ho YY.

Mol Genet Metab. 2007 Feb;90(2):193-8. Epub 2006 Oct 18.

PubMed [citation]

PMID:: 17052934

Functional studies of the T295M mutation causing Glut1 deficiency: glucose efflux preferentially affected by T295M.

Wang D, Yang H, Shi L, Ma L, Fujii T, Engelstad K, Pascual JM, De Vivo DC.

Pediatr Res. 2008 Nov;64(5):538-43. doi: 10.1203/PDR.0b013e318184d2b5.

PubMed [citation]

PMID:: 18614966

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001577959.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

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. For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects SLC2A1 function (PMID: 17052934, 18614966). ClinVar contains an entry for this variant (Variation ID: 207229). This variant is also known as 1063C>T. This missense change has been observed in individual(s) with autosomal dominant GLUT1 deficiency syndrome (PMID: 15622525, 16949238, 20630673). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 295 of the SLC2A1 protein (p.Thr295Met).

#	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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