NM_000151.4(G6PC1):c.1004del (p.Leu335fs) AND Glycogen storage disease due to glucose-6-phosphatase deficiency type IA

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:: RCV003624639.2

Allele description [Variation Report for NM_000151.4(G6PC1):c.1004del (p.Leu335fs)]

NM_000151.4(G6PC1):c.1004del (p.Leu335fs)

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.1004del (p.Leu335fs)

HGVS:

NC_000017.11:g.42911356del
NG_011808.1:g.15559del
NM_000151.4:c.1004delMANE SELECT
NM_001270397.2:c.*396del
NP_000142.1:p.Leu335Argfs
NP_000142.2:p.Leu335fs
LRG_147t1:c.1004del
LRG_147:g.15559del
LRG_147p1:p.Leu335Argfs
NC_000017.10:g.41063373del
NM_000151.2:c.1004delT

Protein change:

L335fs

Molecular consequence:

NM_001270397.2:c.*396del - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000151.4:c.1004del - 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
SCV004380879	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 27, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 7573034, 8182131, 8733042, 10070617, 11949931, 28397058, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004380879

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 27, 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

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

Identification of mutations in the gene for glucose-6-phosphatase, the enzyme deficient in glycogen storage disease type 1a.

Lei KJ, Pan CJ, Shelly LL, Liu JL, Chou JY.

J Clin Invest. 1994 May;93(5):1994-9.

PubMed [citation]

PMID:: 8182131
PMCID:: PMC294308

See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004380879.1

#	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 results in a frameshift in the G6PC gene (p.Leu335Argfs*32). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 23 amino acid(s) of the G6PC protein and extend the protein by 8 additional amino acid residues. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with G6PC-related conditions. 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: Sep 29, 2024

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