NM_001164277.2(SLC37A4):c.83G>T (p.Arg28Leu) AND Glucose-6-phosphate transport defect

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 13, 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:: RCV003618312.2

Allele description [Variation Report for NM_001164277.2(SLC37A4):c.83G>T (p.Arg28Leu)]

NM_001164277.2(SLC37A4):c.83G>T (p.Arg28Leu)

Gene:

SLC37A4:solute carrier family 37 member 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q23.3

Genomic location:

Preferred name:

NM_001164277.2(SLC37A4):c.83G>T (p.Arg28Leu)

HGVS:

NC_000011.10:g.119029287C>A
NG_013331.1:g.6620G>T
NM_001164277.2:c.83G>TMANE SELECT
NM_001164278.2:c.83G>T
NM_001164279.2:c.-172+105G>T
NM_001164280.2:c.83G>T
NM_001467.6:c.83G>T
NP_001157749.1:p.Arg28Leu
NP_001157749.1:p.Arg28Leu
NP_001157750.1:p.Arg28Leu
NP_001157752.1:p.Arg28Leu
NP_001458.1:p.Arg28Leu
NP_001458.1:p.Arg28Leu
LRG_187t1:c.83G>T
LRG_187:g.6620G>T
LRG_187p1:p.Arg28Leu
NC_000011.9:g.118899997C>A
NM_001164277.1:c.83G>T
NM_001467.4:c.83G>T

Protein change:

R28L

Molecular consequence:

NM_001164279.2:c.-172+105G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001164277.2:c.83G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001164278.2:c.83G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001164280.2:c.83G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001467.6:c.83G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Glucose-6-phosphate transport defect (GSD1B)
Synonyms:: Glycogen storage disease type 1B; GSD Ib
Identifiers:: MONDO: MONDO:0009288; MedGen: C0268146; Orphanet: 364; Orphanet: 79259; OMIM: 232220

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004399414	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 13, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 10026167, 12444104, 18337460, 18835800, 27066451, 28224773, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004399414

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 13, 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

Inactivation of the glucose 6-phosphate transporter causes glycogen storage disease type 1b.

Hiraiwa H, Pan CJ, Lin B, Moses SW, Chou JY.

J Biol Chem. 1999 Feb 26;274(9):5532-6.

PubMed [citation]

PMID:: 10026167

Structure-function analysis of the glucose-6-phosphate transporter deficient in glycogen storage disease type Ib.

Chen LY, Pan CJ, Shieh JJ, Chou JY.

Hum Mol Genet. 2002 Dec 1;11(25):3199-207.

PubMed [citation]

PMID:: 12444104

See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004399414.1

#	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 leucine, which is neutral and non-polar, at codon 28 of the SLC37A4 protein (p.Arg28Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SLC37A4-related conditions. 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 SLC37A4 protein function with a positive predictive value of 80%. This variant disrupts the p.Arg28 amino acid residue in SLC37A4. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10026167, 12444104, 18337460, 18835800, 27066451, 28224773). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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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