NM_000151.4(G6PC1):c.821C>T (p.Ala274Val) AND Glycogen storage disease due to glucose-6-phosphatase deficiency type IA

Clinical significance:Likely pathogenic (Last evaluated: Jun 19, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001225198.2

Allele description [Variation Report for NM_000151.4(G6PC1):c.821C>T (p.Ala274Val)]

NM_000151.4(G6PC1):c.821C>T (p.Ala274Val)

Gene:
G6PC1:glucose-6-phosphatase catalytic subunit 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q21.31
Genomic location:
Preferred name:
NM_000151.4(G6PC1):c.821C>T (p.Ala274Val)
HGVS:
  • NC_000017.11:g.42911173C>T
  • NG_011808.1:g.15376C>T
  • NM_000151.4:c.821C>TMANE SELECT
  • NM_001270397.2:c.*213C>T
  • NP_000142.2:p.Ala274Val
  • LRG_147:g.15376C>T
  • NC_000017.10:g.41063190C>T
  • NM_000151.3:c.821C>T
Protein change:
A274V
Molecular consequence:
  • NM_001270397.2:c.*213C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_000151.4:c.821C>T - missense variant - [Sequence Ontology: SO:0001583]

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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001397439Invitaecriteria provided, single submitter
Likely pathogenic
(Jun 19, 2019)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Three novel mutations of the G6PC gene identified in Chinese patients with glycogen storage disease type Ia.

Zheng BX, Lin Q, Li M, Jin Y.

Eur J Pediatr. 2015 Jan;174(1):59-63. doi: 10.1007/s00431-014-2354-y. Epub 2014 Jul 1.

PubMed [citation]
PMID:
24980439
PMCID:
PMC4289013

Late presentation of glycogen storage disease types Ia and III in children with short stature and hepatomegaly.

Quackenbush D, Devito J, Garibaldi L, Buryk M.

J Pediatr Endocrinol Metab. 2018 Mar 28;31(4):473-478. doi: 10.1515/jpem-2017-0209.

PubMed [citation]
PMID:
29374762
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001397439.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces alanine with valine at codon 274 of the G6PC protein (p.Ala274Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs774212157, ExAC 0.004%). This variant has been observed in individual(s) with clinical features of glycogen storage disorder type 1a (GSD1a) (PMID: 24980439, Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0). This variant disrupts the p.Ala274Val amino acid residue in G6PC. Other variant(s) that disrupt this residue have been observed in individuals with G6PC-related conditions (PMID: 29374762), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Oct 7, 2021

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