NM_018972.4(GDAP1):c.368A>G (p.His123Arg) AND Charcot-Marie-Tooth disease axonal type 2K

Clinical significance:Pathogenic (Last evaluated: Aug 9, 2011)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000043549.3

Allele description [Variation Report for NM_018972.4(GDAP1):c.368A>G (p.His123Arg)]

NM_018972.4(GDAP1):c.368A>G (p.His123Arg)

Gene:
GDAP1:ganglioside induced differentiation associated protein 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
8q21.11
Genomic location:
Preferred name:
NM_018972.4(GDAP1):c.368A>G (p.His123Arg)
HGVS:
  • NC_000008.11:g.74360194A>G
  • NG_008787.3:g.44065A>G
  • NM_001040875.4:c.164A>G
  • NM_001362929.2:c.41A>G
  • NM_001362930.2:c.311-1690A>G
  • NM_001362931.2:c.368A>G
  • NM_001362932.2:c.41A>G
  • NM_018972.4:c.368A>GMANE SELECT
  • NP_001035808.1:p.His55Arg
  • NP_001349858.1:p.His14Arg
  • NP_001349860.1:p.His123Arg
  • NP_001349861.1:p.His14Arg
  • NP_061845.2:p.His123Arg
  • LRG_244t1:c.368A>G
  • LRG_244:g.44065A>G
  • NC_000008.10:g.75272429A>G
  • NM_001040875.2:c.164A>G
  • NM_018972.2:c.368A>G
Protein change:
H123R; HIS123ARG
Links:
OMIM: 606598.0018; dbSNP: rs397515442
NCBI 1000 Genomes Browser:
rs397515442
Molecular consequence:
  • NM_001362930.2:c.311-1690A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001040875.4:c.164A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001362929.2:c.41A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001362931.2:c.368A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001362932.2:c.41A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_018972.4:c.368A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Charcot-Marie-Tooth disease axonal type 2K
Synonyms:
CHARCOT-MARIE-TOOTH NEUROPATHY, AXONAL, TYPE 2K; Charcot-Marie-Tooth disease type 2K; Charcot-Marie-Tooth disease, axonal, autosomal recessive, Type 2K
Identifiers:
MONDO: MONDO:0011916; MedGen: C1842983; Orphanet: 99944; OMIM: 607831

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000071290OMIMno assertion criteria providedPathogenic
(Aug 9, 2011)
germlineliterature only

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Dominant GDAP1 mutations cause predominantly mild CMT phenotypes.

Zimoń M, Baets J, Fabrizi GM, Jaakkola E, Kabzińska D, Pilch J, Schindler AB, Cornblath DR, Fischbeck KH, Auer-Grumbach M, Guelly C, Huber N, De Vriendt E, Timmerman V, Suter U, Hausmanowa-Petrusewicz I, Niemann A, Kochański A, De Jonghe P, Jordanova A.

Neurology. 2011 Aug 9;77(6):540-8. doi: 10.1212/WNL.0b013e318228fc70. Epub 2011 Jul 13.

PubMed [citation]
PMID:
21753178
PMCID:
PMC3272385

Details of each submission

From OMIM, SCV000071290.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In 3 affected members of a large Finnish family with dominant CMT2K (607831), Zimon et al. (2011) identified a heterozygous c.358A-G transition in the GDAP1 gene, resulting in a his123-to-arg (H123R) substitution. (The nucleotide numbering was based on a revised transcript.) Four older asymptomatic family members also carried the mutation, indicating incomplete penetrance. The mutation was not found in 280 control individuals. The phenotype was variable, with onset of difficulty walking due to distal muscle weakness and atrophy between 3 and 32 years of age. The disorder was slowly progressive, and all patients remained ambulatory. One patient had proximal weakness. Nerve conduction studies showed an axonal pattern. A heterozygous H123R mutation occurred de novo in a patient of Tunisian origin who was more severely affected and showed delayed motor development; that patient had intermediate results on electrophysiologic studies.

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

Last Updated: Nov 27, 2021

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