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NM_000304.4(PMP22):c.448G>T (p.Gly150Cys)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely pathogenic(1);Uncertain significance(1)

Review status:
criteria provided, conflicting interpretations
Submissions:
3 (Most recent: Jan 7, 2021)
Last evaluated:
Jun 5, 2019
Accession:
VCV000008439.3
Variation ID:
8439
Description:
single nucleotide variant
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NM_000304.4(PMP22):c.448G>T (p.Gly150Cys)

Allele ID
23478
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
17p12
Genomic location
17: 15230952 (GRCh38) GRCh38 UCSC
17: 15134269 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
Q01453:p.Gly150Cys
LRG_263:g.39376G>T
NC_000017.10:g.15134269C>A
... more HGVS
Protein change
G150C
Other names
-
Canonical SPDI
NC_000017.11:15230951:C:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA119624
UniProtKB: Q01453#VAR_006378
OMIM: 601097.0013
dbSNP: rs104894624
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 1 criteria provided, single submitter Dec 1, 2016 RCV000594940.1
Likely pathogenic 1 criteria provided, single submitter Jun 5, 2019 RCV001221866.2
Pathogenic 1 no assertion criteria provided Mar 1, 1998 RCV000008954.5
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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
Uncertain significance
(Dec 01, 2016)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000703278.2
Submitted: (Sep 19, 2018)
Evidence details
Publications
PubMed (2)
Other databases
http://www.egl-eurofins.com/emvc…
Likely pathogenic
(Jun 05, 2019)
criteria provided, single submitter
Method: clinical testing
Charcot-Marie-Tooth disease, type I
Allele origin: germline
Invitae
Accession: SCV001393934.2
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (12)
Comment:
This sequence change replaces glycine with cysteine at codon 150 of the PMP22 protein (p.Gly150Cys). The glycine residue is highly conserved and there is a … (more)
Pathogenic
(Mar 01, 1998)
no assertion criteria provided
Method: literature only
DEJERINE-SOTTAS SYNDROME, AUTOSOMAL DOMINANT
Allele origin: germline
OMIM
Accession: SCV000029164.3
Submitted: (Dec 30, 2010)
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
Application of targeted multi-gene panel testing for the diagnosis of inherited peripheral neuropathy provides a high diagnostic yield with unexpected phenotype-genotype variability. Antoniadi T BMC medical genetics 2015 PMID: 26392352
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
Phenotypic differences between peripheral myelin protein-22 (PMP22) and myelin protein zero (P0) mutations associated with Charcot-Marie-Tooth-related diseases. Shames I Journal of neuropathology and experimental neurology 2003 PMID: 12901701
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
Novel mutations of the peripheral myelin protein 22 gene in two pedigrees with Dejerine-Sottas disease. Ikegami T Human genetics 1998 PMID: 9544841
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
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=PMP22 - - - -

Text-mined citations for rs104894624...

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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 Oct 30, 2021