NM_022041.4(GAN):c.1382C>T (p.Ala461Val) AND Giant axonal neuropathy 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 13, 2022
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:: RCV001347592.7

Allele description [Variation Report for NM_022041.4(GAN):c.1382C>T (p.Ala461Val)]

NM_022041.4(GAN):c.1382C>T (p.Ala461Val)

Gene:

GAN:gigaxonin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16q23.2

Genomic location:

Preferred name:

NM_022041.4(GAN):c.1382C>T (p.Ala461Val)

HGVS:

NC_000016.10:g.81365358C>T
NG_009007.1:g.55393C>T
NM_001377486.1:c.743C>T
NM_022041.4:c.1382C>TMANE SELECT
NP_001364415.1:p.Ala248Val
NP_071324.1:p.Ala461Val
LRG_242:g.55393C>T
NC_000016.9:g.81398963C>T

Protein change:

A248V

Links:

dbSNP: rs753748994

NCBI 1000 Genomes Browser:

rs753748994

Molecular consequence:

NM_001377486.1:c.743C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_022041.4:c.1382C>T - 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
SCV001541861	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 13, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29876741, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001541861

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 13, 2022)

germline

clinical testing

PubMed (2)
[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

Two novel mutations in the GAN gene causing giant axonal neuropathy.

Normendez-Martínez MI, Monterde-Cruz L, Martínez R, Marquez-Harper M, Esquitin-Garduño N, Valdes-Flores M, Casas-Avila L, de Leon-Suarez VP, Romero-Díaz VJ, Hidalgo-Bravo A.

World J Pediatr. 2018 Jun;14(3):298-304. doi: 10.1007/s12519-018-0140-z. Epub 2018 Jun 6. Review.

PubMed [citation]

PMID:: 29876741

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, SCV001541861.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

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 not expected to disrupt GAN protein function. 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. ClinVar contains an entry for this variant (Variation ID: 1043475). This missense change has been observed in individual(s) with giant axonal neuropathy (PMID: 29876741). This variant is present in population databases (rs753748994, gnomAD 0.007%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 461 of the GAN protein (p.Ala461Val).

#	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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