NM_006516.4(SLC2A1):c.880T>C (p.Ser294Pro) AND GLUT1 deficiency syndrome 1, autosomal recessive

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 27, 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:: RCV003518722.2

Allele description [Variation Report for NM_006516.4(SLC2A1):c.880T>C (p.Ser294Pro)]

NM_006516.4(SLC2A1):c.880T>C (p.Ser294Pro)

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.880T>C (p.Ser294Pro)

HGVS:

NC_000001.11:g.42929302A>G
NG_008232.1:g.34875T>C
NG_090763.1:g.818A>G
NG_090764.1:g.175A>G
NM_006516.4:c.880T>CMANE SELECT
NP_006507.2:p.Ser294Pro
NP_006507.2:p.Ser294Pro
LRG_1132t1:c.880T>C
LRG_1132:g.34875T>C
LRG_1132p1:p.Ser294Pro
NC_000001.10:g.43394973A>G
NM_006516.3:c.880T>C

Protein change:

S294P

Molecular consequence:

NM_006516.4:c.880T>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
SCV004291802	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 27, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 20830593, 26193382, 28556183, 21649651, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004291802

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 27, 2023)

germline

clinical testing

PubMed (5)
[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

Excellent response to acetazolamide in a case of paroxysmal dyskinesias due to GLUT1-deficiency.

Anheim M, Maillart E, Vuillaumier-Barrot S, Flamand-Rouvière C, Pineau F, Ewenczyk C, Riant F, Apartis E, Roze E.

J Neurol. 2011 Feb;258(2):316-7. doi: 10.1007/s00415-010-5702-5. Epub 2010 Sep 10. No abstract available.

PubMed [citation]

PMID:: 20830593

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 (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004291802.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 294 of the SLC2A1 protein (p.Ser294Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of autosomal dominant GLUT1 deficiency (PMID: 20830593, 26193382, 28556183). 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 with a positive predictive value of 95%. This variant disrupts the p.Ser294 amino acid residue in SLC2A1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 21649651; Invitae). 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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