NM_001164277.2(SLC37A4):c.83G>A (p.Arg28His) AND Glucose-6-phosphate transport defect

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Aug 15, 2018)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
4 submissions [Details]
Record status:
current
Accession:
RCV000007345.6

Allele description [Variation Report for NM_001164277.2(SLC37A4):c.83G>A (p.Arg28His)]

NM_001164277.2(SLC37A4):c.83G>A (p.Arg28His)

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>A (p.Arg28His)
HGVS:
  • NC_000011.10:g.119029287C>T
  • NG_013331.1:g.6620G>A
  • NM_001164277.1:c.83G>A
  • NM_001164277.2:c.83G>A
  • NM_001164278.2:c.83G>A
  • NM_001164279.2:c.-172+105G>A
  • NM_001164280.2:c.83G>A
  • NM_001467.6:c.83G>A
  • NP_001157749.1:p.Arg28His
  • NP_001157749.1:p.Arg28His
  • NP_001157750.1:p.Arg28His
  • NP_001157752.1:p.Arg28His
  • NP_001458.1:p.Arg28His
  • LRG_187t1:c.83G>A
  • LRG_187:g.6620G>A
  • LRG_187p1:p.Arg28His
  • NC_000011.9:g.118899997C>T
Protein change:
R28H; ARG28HIS
Links:
UniProtKB/Swiss-Prot: VAR_016840; OMIM: 602671.0013; dbSNP: rs121908978
NCBI 1000 Genomes Browser:
rs121908978
Molecular consequence:
  • NM_001164279.2:c.-172+105G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001164277.1:c.83G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001164277.2:c.83G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001164278.2:c.83G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001164280.2:c.83G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001467.6:c.83G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000027543OMIMno assertion criteria providedPathogenic
(Feb 26, 1999)
germlineliterature only

PubMed (1)
[See all records that cite this PMID]

SCV000793511Counsylcriteria provided, single submitter
Likely pathogenic
(Aug 18, 2017)
unknownclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Citation Link,

SCV000960555Invitaecriteria provided, single submitter
Pathogenic
(Aug 15, 2018)
germlineclinical testing

PubMed (8)
[See all records that cite these PMIDs]

SCV001457673Natera, Inc.no assertion criteria providedPathogenic
(Sep 16, 2020)
germlineclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Identification of glucose-6-phosphate transporter as a key regulator functioning at the autophagy initiation step.

Ahn HH, Oh Y, Lee H, Lee W, Chang JW, Pyo HK, Nah do H, Jung YK.

FEBS Lett. 2015 Jul 22;589(16):2100-9. doi: 10.1016/j.febslet.2015.05.018. Epub 2015 May 15.

PubMed [citation]
PMID:
25982172

Structural requirements for the stability and microsomal transport activity of the human glucose 6-phosphate transporter.

Chen LY, Lin B, Pan CJ, Hiraiwa H, Chou JY.

J Biol Chem. 2000 Nov 3;275(44):34280-6.

PubMed [citation]
PMID:
10940311
See all PubMed Citations (11)

Details of each submission

From OMIM, SCV000027543.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In 2 of 9 families with GSD Ib (GSD1B; 232220), Hiraiwa et al. (1999) identified a G-to-A transition at nucleotide 252 of the G6PT1 gene, resulting in an arg28-to-his (R28H) mutation. They demonstrated that this mutation resulted in inactive G6P transport.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

From Counsyl, SCV000793511.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV000960555.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)

Description

This sequence change replaces arginine with histidine at codon 28 of the SLC37A4 protein (p.Arg28His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs121908978, ExAC 0.006%). This variant has been observed to be homozygous or in combination with another SLC37A4 variant in several individuals affected with glycogen storage disease (PMID: 10026167, 27066451, 28224773). ClinVar contains an entry for this variant (Variation ID: 6933). Experimental studies have shown that this missense change results in a SLC37A4 protein with reduced G6P uptake and reduced phosphohydrolase activity (PMID: 10026167, 12444104, 18835800, 18337460). The observation of one or more missense substitutions at this codon (p.Arg28His and p.Arg28Cys) in affected individuals suggests that this may be a clinically significant residue (PMID: 10518030, 10026167, 27066451, 28224773). For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Natera, Inc., SCV001457673.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 25, 2021

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