NM_001164277.2(SLC37A4):c.899G>A (p.Arg300His) AND Glucose-6-phosphate transport defect

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Dec 2, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001388583.7

Allele description [Variation Report for NM_001164277.2(SLC37A4):c.899G>A (p.Arg300His)]

NM_001164277.2(SLC37A4):c.899G>A (p.Arg300His)

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.899G>A (p.Arg300His)

HGVS:

NC_000011.10:g.119026052C>T
NG_013331.1:g.9854G>A
NM_001164277.2:c.899G>AMANE SELECT
NM_001164278.2:c.899G>A
NM_001164279.2:c.680G>A
NM_001164280.2:c.899G>A
NM_001467.6:c.899G>A
NP_001157749.1:p.Arg300His
NP_001157749.1:p.Arg300His
NP_001157750.1:p.Arg300His
NP_001157751.1:p.Arg227His
NP_001157752.1:p.Arg300His
NP_001458.1:p.Arg300His
LRG_187t1:c.899G>A
LRG_187:g.9854G>A
LRG_187p1:p.Arg300His
NC_000011.9:g.118896762C>T
NM_001164277.1:c.899G>A

Protein change:

R227H

Links:

UniProtKB/Swiss-Prot: VAR_025599; dbSNP: rs193302903

NCBI 1000 Genomes Browser:

rs193302903

Molecular consequence:

NM_001164277.2:c.899G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001164278.2:c.899G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001164279.2:c.680G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001164280.2:c.899G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001467.6:c.899G>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:: MONDO: MONDO:0009288; MedGen: C0268146; Orphanet: 364; Orphanet: 79259; OMIM: 232220

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001589635	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 2, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 9781688, 15906092, 10940311, 12444104, 28492532
SCV004099067	Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 5, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004202441	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 3, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001589635

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 2, 2023)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV004099067

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jul 5, 2023)

germline

clinical testing

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

SCV004202441

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 3, 2023)

unknown

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Structure and mutation analysis of the glycogen storage disease type 1b gene.

Marcolongo P, Barone V, Priori G, Pirola B, Giglio S, Biasucci G, Zammarchi E, Parenti G, Burchell A, Benedetti A, Sorrentino V.

FEBS Lett. 1998 Oct 2;436(2):247-50. Erratum in: FEBS Lett 1999 Feb 26;445(2-3):451.

PubMed [citation]

PMID:: 9781688

Genotype/phenotype correlation in glycogen storage disease type 1b: a multicentre study and review of the literature.

Melis D, Fulceri R, Parenti G, Marcolongo P, Gatti R, Parini R, Riva E, Della Casa R, Zammarchi E, Andria G, Benedetti A.

Eur J Pediatr. 2005 Aug;164(8):501-8. Epub 2005 May 19. Review.

PubMed [citation]

PMID:: 15906092

See all PubMed Citations (6)

Details of each submission

From Invitae, SCV001589635.4

#	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 arginine, which is basic and polar, with histidine, which is basic and polar, at codon 300 of the SLC37A4 protein (p.Arg300His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal recessive SLC37A4-related conditions (PMID: 9781688, 15906092). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 68294). 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%. Experimental studies have shown that this missense change affects SLC37A4 function (PMID: 10940311, 12444104). 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

From Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center, SCV004099067.1

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

Description

PS3, PM2, PM3, PM5

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004202441.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 15, 2024

ClinVar

Relating variation to medicine