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NM_000304.4(PMP22):c.449G>A (p.Gly150Asp)

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Interpretation:
Pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
3 (Most recent: Jan 7, 2021)
Last evaluated:
Jul 15, 2019
Accession:
VCV000245805.5
Variation ID:
245805
Description:
single nucleotide variant
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NM_000304.4(PMP22):c.449G>A (p.Gly150Asp)

Allele ID
245013
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
17p12
Genomic location
17: 15134268 (GRCh37) GRCh37 UCSC
17: 15230951 (GRCh38) GRCh38 UCSC
HGVS
Nucleotide Protein Molecular
consequence
Q01453:p.Gly150Asp
LRG_263t1:c.449G>A
LRG_263:g.39377G>A
... more HGVS
Protein change
G150D
Other names
-
Canonical SPDI
NC_000017.11:15230950:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA10584542
UniProtKB: Q01453#VAR_006379
dbSNP: rs879253954
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 1 criteria provided, single submitter Jan 4, 2017 RCV000236879.2
Pathogenic 1 criteria provided, single submitter Jul 15, 2019 RCV001209293.1
Uncertain significance 1 no assertion criteria provided - RCV000790159.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
PMP22 Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
295 389

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Jan 04, 2017)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000292940.10
Submitted: (Jan 29, 2019)
Evidence details
Comment:
The G150D mutation in the PMP22 gene has been reported previously in two patients with Dejerine-Sottas neuropathy (Ionasescu et al., 1997); the patients were mother … (more)
Pathogenic
(Jul 15, 2019)
criteria provided, single submitter
Method: clinical testing
Charcot-Marie-Tooth disease, type I
Allele origin: germline
Invitae
Accession: SCV001380720.2
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (10)
Comment:
This sequence change replaces glycine with aspartic acid at codon 150 of the PMP22 protein (p.Gly150Asp). The glycine residue is highly conserved and there is … (more)
Uncertain significance
(-)
no assertion criteria provided
Method: literature only
Dejerine-Sottas disease
Allele origin: germline
Inherited Neuropathy Consortium
Accession: SCV000929550.1
Submitted: (Jul 10, 2019)
Evidence details
Publications
PubMed (1)

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
Conformational Stability and Pathogenic Misfolding of the Integral Membrane Protein PMP22. Schlebach JP Journal of the American Chemical Society 2015 PMID: 26102530
Rer1 and calnexin regulate endoplasmic reticulum retention of a peripheral myelin protein 22 mutant that causes type 1A Charcot-Marie-Tooth disease. Hara T Scientific reports 2014 PMID: 25385046
The peripheral neuropathy-linked Trembler and Trembler-J mutant forms of peripheral myelin protein 22 are folding-destabilized. Myers JK Biochemistry 2008 PMID: 18795802
Glycan-independent role of calnexin in the intracellular retention of Charcot-Marie-tooth 1A Gas3/PMP22 mutants. Fontanini A The Journal of biological chemistry 2005 PMID: 15537650
Recessive, but not dominant, mutations in peripheral myelin protein 22 gene show unique patterns of aggregation and intracellular trafficking. Liu N Neurobiology of disease 2004 PMID: 15474367
Exposure at the cell surface is required for gas3/PMP22 To regulate both cell death and cell spreading: implication for the Charcot-Marie-Tooth type 1A and Dejerine-Sottas diseases. Brancolini C Molecular biology of the cell 2000 PMID: 10982389
Impaired intracellular trafficking is a common disease mechanism of PMP22 point mutations in peripheral neuropathies. Naef R Neurobiology of disease 1999 PMID: 10078969
Overloaded endoplasmic reticulum-Golgi compartments, a possible pathomechanism of peripheral neuropathies caused by mutations of the peripheral myelin protein PMP22. D'Urso D The Journal of neuroscience : the official journal of the Society for Neuroscience 1998 PMID: 9425015
Dejerine-Sottas neuropathy in mother and son with same point mutation of PMP22 gene. Ionasescu VV Muscle & nerve 1997 PMID: 8995589
Trembler mouse carries a point mutation in a myelin gene. Suter U Nature 1992 PMID: 1552943

Text-mined citations for rs879253954...

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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 Nov 27, 2021