NM_053013.4(ENO3):c.1121G>A (p.Gly374Glu) AND Glycogen storage disease due to muscle beta-enolase deficiency

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Sep 27, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000018093.32

Allele description [Variation Report for NM_053013.4(ENO3):c.1121G>A (p.Gly374Glu)]

NM_053013.4(ENO3):c.1121G>A (p.Gly374Glu)

Gene:

ENO3:enolase 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p13.2

Genomic location:

Preferred name:

NM_053013.4(ENO3):c.1121G>A (p.Gly374Glu)

HGVS:

NC_000017.11:g.4956626G>A
NG_012063.2:g.15536G>A
NM_001193503.2:c.992G>A
NM_001976.5:c.1121G>A
NM_053013.4:c.1121G>AMANE SELECT
NP_001180432.1:p.Gly331Glu
NP_001967.3:p.Gly374Glu
NP_443739.3:p.Gly374Glu
NC_000017.10:g.4859921G>A
NM_053013.3:c.1121G>A
P13929:p.Gly374Glu

Protein change:

G331E; GLY374GLU

Links:

UniProtKB: P13929#VAR_020621; OMIM: 131370.0002; dbSNP: rs121918404

NCBI 1000 Genomes Browser:

rs121918404

Molecular consequence:

NM_001193503.2:c.992G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001976.5:c.1121G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_053013.4:c.1121G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Glycogen storage disease due to muscle beta-enolase deficiency (GSD13)
Synonyms:: GSD XIII; Glycogen storage disease type 13; Enolase-beta deficiency; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0013046; MedGen: C2752027; Orphanet: 99849; OMIM: 612932

Recent activity

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Homo sapiens eukaryotic translation initiation factor 4 gamma, 1 (EIF4G1), trans...
Homo sapiens eukaryotic translation initiation factor 4 gamma, 1 (EIF4G1), transcript variant 4, mRNA
gi|38201624|ref|NM_198242.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000038372	OMIM	no assertion criteria provided	Pathogenic (Aug 1, 2001)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV002171587	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 27, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 11506403, 18070103, 28492532
SCV002790833	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 4, 2022)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000038372

OMIM

no assertion criteria provided

Pathogenic
(Aug 1, 2001)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV002171587

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 27, 2022)

germline

clinical testing

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

SCV002790833

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 4, 2022)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Beta-enolase deficiency, a new metabolic myopathy of distal glycolysis.

Comi GP, Fortunato F, Lucchiari S, Bordoni A, Prelle A, Jann S, Keller A, Ciscato P, Galbiati S, Chiveri L, Torrente Y, Scarlato G, Bresolin N.

Ann Neurol. 2001 Aug;50(2):202-7.

PubMed [citation]

PMID:: 11506403

Effects of the G376E and G157D mutations on the stability of yeast enolase--a model for human muscle enolase deficiency.

Zhao S, Choy BS, Kornblatt MJ.

FEBS J. 2008 Jan;275(1):97-106. Epub 2007 Dec 7.

PubMed [citation]

PMID:: 18070103

See all PubMed Citations (4)

Details of each submission

From OMIM, SCV000038372.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

For discussion of the gly374-to-glu (G374E) mutation in the ENO3 gene that was found in compound heterozygous state in a patient with adult onset of exercise-induced myalgias, generalized muscle weakness, and fatigability (GSD13; 612932) by Comi et al. (2001), see 131370.0001.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002171587.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 374 of the ENO3 protein (p.Gly374Glu). This variant is present in population databases (rs121918404, gnomAD 0.03%). This missense change has been observed in individual(s) with clinical features of ENO3-related conditions (PMID: 11506403). ClinVar contains an entry for this variant (Variation ID: 16618). 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 ENO3 protein function. Experimental studies have shown that this missense change affects ENO3 function (PMID: 18070103). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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

From Fulgent Genetics, Fulgent Genetics, SCV002790833.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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