NM_000151.4(G6PC1):c.788del (p.Lys263fs) AND Glycogen storage disease due to glucose-6-phosphatase deficiency type IA

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 5, 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:: RCV002651266.2

Allele description [Variation Report for NM_000151.4(G6PC1):c.788del (p.Lys263fs)]

NM_000151.4(G6PC1):c.788del (p.Lys263fs)

Gene:

G6PC1:glucose-6-phosphatase catalytic subunit 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

17q21.31

Genomic location:

Preferred name:

NM_000151.4(G6PC1):c.788del (p.Lys263fs)

HGVS:

NC_000017.11:g.42911140del
NG_011808.1:g.15343del
NM_000151.4:c.788delMANE SELECT
NM_001270397.2:c.*180del
NP_000142.1:p.Lys263Argfs
NP_000142.2:p.Lys263fs
LRG_147t1:c.788del
LRG_147:g.15343del
LRG_147p1:p.Lys263Argfs
NC_000017.10:g.41063156del
NC_000017.10:g.41063157del
NM_000151.2:c.788delA

Protein change:

K263fs

Molecular consequence:

NM_001270397.2:c.*180del - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000151.4:c.788del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Glycogen storage disease due to glucose-6-phosphatase deficiency type IA (GSD1A)
Synonyms:: GSD Ia; Glycogen storage disease type 1A; Von Gierke disease; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009287; MedGen: C2919796; Orphanet: 364; Orphanet: 79258; OMIM: 232200

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003517526	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 5, 2023)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 10737986, 7573034, 8182131, 8733042, 10070617, 11949931, 28397058, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003517526

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 5, 2023)

germline

clinical testing

PubMed (8)
[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

Identification of a novel mutation (867delA) in the glucose-6-phosphatase gene in two siblings with glycogen storage disease type Ia with different phenotypes.

Rake JP, ten Berge AM, Visser G, Verlind E, Niezen-Koning KE, Buys CH, Smit GP, Scheffer H.

Hum Mutat. 2000 Apr;15(4):381.

PubMed [citation]

PMID:: 10737986

Genetic basis of glycogen storage disease type 1a: prevalent mutations at the glucose-6-phosphatase locus.

Lei KJ, Chen YT, Chen H, Wong LJ, Liu JL, McConkie-Rosell A, Van Hove JL, Ou HC, Yeh NJ, Pan LY, et al.

Am J Hum Genet. 1995 Oct;57(4):766-71.

PubMed [citation]

PMID:: 7573034
PMCID:: PMC1801521

See all PubMed Citations (8)

Details of each submission

From Invitae, SCV003517526.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

This sequence change creates a premature translational stop signal (p.Lys263Argfs*38) in the G6PC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 95 amino acid(s) of the G6PC protein. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with glycogen storage disease (PMID: 10737986). This variant is also known as 867delA. ClinVar contains an entry for this variant (Variation ID: 2197137). This variant disrupts a region of the G6PC protein in which other variant(s) (p.Gln347*) have been determined to be pathogenic (PMID: 7573034, 8182131, 8733042, 10070617, 11949931, 28397058). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it 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: Feb 20, 2024

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