NM_022041.4(GAN):c.374T>C (p.Leu125Ser) AND Giant axonal neuropathy 1

This record was updated by the submitter. Please see the current version.

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 15, 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:: RCV000533057.4

Allele description

NM_022041.4(GAN):c.374T>C (p.Leu125Ser)

Gene:

GAN:gigaxonin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16q23.2

Genomic location:

Preferred name:

NM_022041.4(GAN):c.374T>C (p.Leu125Ser)

HGVS:

NC_000016.10:g.81354496T>C
NG_009007.1:g.44531T>C
NM_001377486.1:c.-266T>C
NM_022041.4:c.374T>CMANE SELECT
NP_071324.1:p.Leu125Ser
NP_071324.1:p.Leu125Ser
LRG_242t1:c.374T>C
LRG_242:g.44531T>C
LRG_242p1:p.Leu125Ser
NC_000016.9:g.81388101T>C
NM_022041.3:c.374T>C

Protein change:

L125S

Links:

dbSNP: rs1555511093

NCBI 1000 Genomes Browser:

rs1555511093

Molecular consequence:

NM_001377486.1:c.-266T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_022041.4:c.374T>C - 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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000640435	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Mar 15, 2023)	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

SCV000640435

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Mar 15, 2023)

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 Invitae, SCV000640435.4

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

Description

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. 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 GAN protein function. ClinVar contains an entry for this variant (Variation ID: 465396). This missense change has been observed in individual(s) with clinical features of giant axonal neuropathy (Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 125 of the GAN protein (p.Leu125Ser).

#	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: Feb 20, 2024

ClinVar

Relating variation to medicine