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

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
6 (Most recent: Jul 12, 2021)
Last evaluated:
Aug 17, 2020
Accession:
VCV000050558.7
Variation ID:
50558
Description:
single nucleotide variant
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NM_018972.4(GDAP1):c.368A>G (p.His123Arg)

Allele ID
59596
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
8q21.11
Genomic location
8: 74360194 (GRCh38) GRCh38 UCSC
8: 75272429 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000008.10:g.75272429A>G
NC_000008.11:g.74360194A>G
NM_018972.4:c.368A>G MANE Select NP_061845.2:p.His123Arg missense
... more HGVS
Protein change
H123R, H55R, H14R
Other names
-
Canonical SPDI
NC_000008.11:74360193:A:G
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
OMIM: 606598.0018
dbSNP: rs397515442
ClinGen: CA263218
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic/Likely pathogenic 2 criteria provided, multiple submitters, no conflicts Aug 18, 2016 RCV000254797.2
Pathogenic 1 criteria provided, single submitter Aug 17, 2020 RCV000696667.3
Pathogenic 1 no assertion criteria provided Aug 9, 2011 RCV000043549.3
Conflicting interpretations of pathogenicity 2 no assertion criteria provided Aug 14, 2019 RCV000857206.2
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
GDAP1 - - GRCh38
GRCh37
394 423

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Nov 25, 2014)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Clinical Genetics Karolinska University Hospital,Karolinska University Hospital
Accession: SCV001450116.1
Submitted: (Nov 26, 2020)
Evidence details
Pathogenic
(Aug 18, 2016)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000321716.7
Submitted: (Jan 29, 2019)
Evidence details
Comment:
The H123R pathogenic variant in the GDAP1 gene has been reported previously in multiple unrelatedfamilies with autosomal dominant Charcot-Marie-Tooth (CMT) disease (Zimon et al., 2011; … (more)
Pathogenic
(Aug 17, 2020)
criteria provided, single submitter
Method: clinical testing
Charcot-Marie-Tooth disease, type 4A
Allele origin: germline
Invitae
Accession: SCV000825239.3
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (6)
Comment:
This sequence change replaces histidine with arginine at codon 123 of the GDAP1 protein (p.His123Arg). The histidine residue is highly conserved and there is a … (more)
Pathogenic
(Aug 09, 2011)
no assertion criteria provided
Method: literature only
CHARCOT-MARIE-TOOTH DISEASE, AUTOSOMAL DOMINANT, TYPE 2K
Allele origin: germline
OMIM
Accession: SCV000071290.2
Submitted: (May 28, 2013)
Evidence details
Publications
PubMed (1)
Uncertain significance
(Aug 14, 2019)
no assertion criteria provided
Method: research
Charcot-Marie-Tooth disease
Allele origin: germline
Genesis Genome Database
Accession: SCV000999788.1
Submitted: (Aug 19, 2019)
Evidence details
Pathogenic
(Mar 30, 2017)
no assertion criteria provided
Method: literature only
None
Allele origin: germline
GeneReviews
Accession: SCV001750195.1
Submitted: (Jul 12, 2021)
Evidence details
Publications
PubMed (1)
BookShelf: NBK1539

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
CMT-linked loss-of-function mutations in GDAP1 impair store-operated Ca<sup>2+</sup> entry-stimulated respiration. González-Sánchez P Scientific reports 2017 PMID: 28220846
<i>GDAP1</i>-Related Hereditary Motor and Sensory Neuropathy Bird TD - 2017 PMID: 20301711
GDAP1 mutations in Italian axonal Charcot-Marie-Tooth patients: Phenotypic features and clinical course. Pezzini I Neuromuscular disorders : NMD 2016 PMID: 26525999
Targeted next-generation sequencing reveals further genetic heterogeneity in axonal Charcot-Marie-Tooth neuropathy and a mutation in HSPB1. Ylikallio E European journal of human genetics : EJHG 2014 PMID: 23963299
Dominant GDAP1 founder mutation is a common cause of axonal Charcot-Marie-Tooth disease in Finland. Auranen M Neurogenetics 2013 PMID: 23456260
Dominant GDAP1 mutations cause predominantly mild CMT phenotypes. Zimoń M Neurology 2011 PMID: 21753178

Text-mined citations for rs397515442...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jul 15, 2021