NM_000158.4(GBE1):c.718A>G (p.Ile240Val) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 4, 2020
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:: RCV001363525.2

Allele description [Variation Report for NM_000158.4(GBE1):c.718A>G (p.Ile240Val)]

NM_000158.4(GBE1):c.718A>G (p.Ile240Val)

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.718A>G (p.Ile240Val)

HGVS:

NC_000003.12:g.81646456T>C
NG_011810.1:g.120345A>G
NM_000158.4:c.718A>GMANE SELECT
NP_000149.4:p.Ile240Val
NC_000003.11:g.81695607T>C

Protein change:

I240V

Links:

dbSNP: rs868766244

NCBI 1000 Genomes Browser:

rs868766244

Molecular consequence:

NM_000158.4:c.718A>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

Recent activity

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ribonuclease kappa [Homo sapiens]
ribonuclease kappa [Homo sapiens]
gi|1844066244|ref|NP_001004333.3|

Protein
Mus musculus DDB1 and CUL4 associated factor 4 (Dcaf4), transcript variant 2, mR...
Mus musculus DDB1 and CUL4 associated factor 4 (Dcaf4), transcript variant 2, mRNA
gi|259155343|ref|NM_030246.2|

Nucleotide
ninjurin-2 isoform 1 [Mus musculus]
ninjurin-2 isoform 1 [Mus musculus]
gi|7710070|ref|NP_057927.1|

Protein
PREDICTED: Rattus norvegicus hephaestin (Heph), transcript variant X7, mRNA
PREDICTED: Rattus norvegicus hephaestin (Heph), transcript variant X7, mRNA
gi|2678974835|ref|XM_039099422.2|

Nucleotide
hephaestin isoform X1 [Rattus norvegicus]
hephaestin isoform X1 [Rattus norvegicus]
gi|1958806507|ref|XP_038955350.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001559641	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 4, 2020)	germline	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

SCV001559641

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 4, 2020)

germline

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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, SCV001559641.1

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

Description

This sequence change replaces isoleucine with valine at codon 240 of the GBE1 protein (p.Ile240Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with GBE1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Not Available; PolyPhen-2: Benign; Align-GVGD: Not Available. The isoleucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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

Last Updated: Sep 29, 2024

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