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

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:
RCV000533057.5

Allele description [Variation Report for NM_022041.4(GAN):c.374T>C (p.Leu125Ser)]

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000640435Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Mar 15, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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, SCV000640435.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical 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).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024