NM_000151.4(G6PC1):c.626A>G (p.Tyr209Cys) AND Glycogen storage disease due to glucose-6-phosphatase deficiency type IA

Clinical significance:Likely pathogenic (Last evaluated: Feb 13, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001049851.2

Allele description [Variation Report for NM_000151.4(G6PC1):c.626A>G (p.Tyr209Cys)]

NM_000151.4(G6PC1):c.626A>G (p.Tyr209Cys)

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.626A>G (p.Tyr209Cys)
HGVS:
  • NC_000017.11:g.42910978A>G
  • NG_011808.1:g.15181A>G
  • NM_000151.4:c.626A>GMANE SELECT
  • NM_001270397.2:c.*18A>G
  • NP_000142.2:p.Tyr209Cys
  • LRG_147:g.15181A>G
  • NC_000017.10:g.41062995A>G
  • NM_000151.3:c.626A>G
Protein change:
Y209C
Molecular consequence:
  • NM_001270397.2:c.*18A>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_000151.4:c.626A>G - 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
SCV001213924Invitaecriteria provided, single submitter
Likely pathogenic
(Feb 13, 2020)
germlineclinical testing

PubMed (2)
[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

Glycogen storage disease type Ia in Argentina: two novel glucose-6-phosphatase mutations affecting protein stability.

Angaroni CJ, de Kremer RD, ArgaraƱa CE, Paschini-Capra AE, Giner-Ayala AN, Pezza RJ, Pan CJ, Chou JY.

Mol Genet Metab. 2004 Nov;83(3):276-9.

PubMed [citation]
PMID:
15542400

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001213924.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces tyrosine with cysteine at codon 209 of the G6PC protein (p.Tyr209Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with clinical features or a diagnosis of GSD Ia (PMID: 15542400, Invitae). 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 G6PC protein function. 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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