NM_022041.4(GAN):c.1477G>A (p.Glu493Lys) AND Giant axonal neuropathy 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 28, 2023
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:: RCV000641262.7

Allele description [Variation Report for NM_022041.4(GAN):c.1477G>A (p.Glu493Lys)]

NM_022041.4(GAN):c.1477G>A (p.Glu493Lys)

Gene:

GAN:gigaxonin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16q23.2

Genomic location:

Preferred name:

NM_022041.4(GAN):c.1477G>A (p.Glu493Lys)

HGVS:

NC_000016.10:g.81365453G>A
NG_009007.1:g.55488G>A
NM_001377486.1:c.838G>A
NM_022041.4:c.1477G>AMANE SELECT
NP_001364415.1:p.Glu280Lys
NP_071324.1:p.Glu493Lys
NP_071324.1:p.Glu493Lys
LRG_242t1:c.1477G>A
LRG_242:g.55488G>A
LRG_242p1:p.Glu493Lys
NC_000016.9:g.81399058G>A
NM_022041.3:c.1477G>A

Protein change:

E280K

Links:

dbSNP: rs780427229

NCBI 1000 Genomes Browser:

rs780427229

Molecular consequence:

NM_001377486.1:c.838G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_022041.4:c.1477G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Giant axonal neuropathy 1 (GAN1)
Synonyms:: GIANT AXONAL NEUROPATHY 1, AUTOSOMAL RECESSIVE
Identifiers:: MONDO: MONDO:0009749; MedGen: C1850386; Orphanet: 643; OMIM: 256850

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000762901	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 28, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 30532362, 31655922, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000762901

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 28, 2023)

germline

clinical testing

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

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

Giant Axonal Neuropathy: Clinical, Radiological, and Genetic Features.

Garg M, Kulkarni SD, Hegde AU, Desai M, Sayed RJ.

Ann Indian Acad Neurol. 2018 Oct-Dec;21(4):304-308. doi: 10.4103/aian.AIAN_82_18.

PubMed [citation]

PMID:: 30532362
PMCID:: PMC6238561

Giant axonal neuropathy: a multicenter retrospective study with genotypic spectrum expansion.

Echaniz-Laguna A, Cuisset JM, Guyant-Marechal L, Aubourg P, Kremer L, Baaloul N, Verloes A, Beladgham K, Perrot J, Francou B, Latour P.

Neurogenetics. 2020 Jan;21(1):29-37. doi: 10.1007/s10048-019-00596-z. Epub 2019 Oct 26.

PubMed [citation]

PMID:: 31655922

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000762901.4

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

Description

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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 533935). This missense change has been observed in individuals with giant axonal neuropathy (PMID: 30532362, 31655922). This variant is present in population databases (rs780427229, gnomAD 0.002%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 493 of the GAN protein (p.Glu493Lys).

#	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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