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NM_000158.4(GBE1):c.1634A>G (p.His545Arg) AND multiple conditions

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jan 29, 2024
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:
RCV003764519.2

Allele description [Variation Report for NM_000158.4(GBE1):c.1634A>G (p.His545Arg)]

NM_000158.4(GBE1):c.1634A>G (p.His545Arg)

Gene:
GBE1:1,4-alpha-glucan branching enzyme 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3p12.2
Genomic location:
Preferred name:
NM_000158.4(GBE1):c.1634A>G (p.His545Arg)
HGVS:
  • NC_000003.12:g.81537080T>C
  • NG_011810.1:g.229721A>G
  • NM_000158.4:c.1634A>GMANE SELECT
  • NP_000149.4:p.His545Arg
  • NC_000003.11:g.81586231T>C
  • Q04446:p.His545Arg
Nucleotide change:
c.1634A>G
Protein change:
H545R; HIS545ARG
Links:
UniProtKB: Q04446#VAR_022435; OMIM: 607839.0010; dbSNP: rs137852889
NCBI 1000 Genomes Browser:
rs137852889
Molecular consequence:
  • NM_000158.4:c.1634A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Glycogen storage disease, type IV (GSD4)
Synonyms:
GBE1 DEFICIENCY; GLYCOGENOSIS IV; GSD IV; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009292; MedGen: C0017923; Orphanet: 367; OMIM: 232500
Name:
Glycogen storage disease IV, classic hepatic
Synonyms:
GSD IV, CLASSIC HEPATIC
Identifiers:
MedGen: C1856301

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV004569776Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Likely pathogenic
(Jan 29, 2024)
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

Clinical and genetic heterogeneity of branching enzyme deficiency (glycogenosis type IV).

Bruno C, van Diggelen OP, Cassandrini D, Gimpelev M, Giuffrè B, Donati MA, Introvini P, Alegria A, Assereto S, Morandi L, Mora M, Tonoli E, Mascelli S, Traverso M, Pasquini E, Bado M, Vilarinho L, van Noort G, Mosca F, DiMauro S, Zara F, Minetti C.

Neurology. 2004 Sep 28;63(6):1053-8.

PubMed [citation]
PMID:
15452297

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004569776.1

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

Description

This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 545 of the GBE1 protein (p.His545Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with glycogen storage disease (PMID: 15452297). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 2785). 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 GBE1 protein function with a positive predictive value of 95%. 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: Sep 29, 2024