NM_000530.8(MPZ):c.499G>A (p.Gly167Arg) AND Charcot-Marie-Tooth disease, type I

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 24, 2021
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:: RCV001053594.14

Allele description [Variation Report for NM_000530.8(MPZ):c.499G>A (p.Gly167Arg)]

NM_000530.8(MPZ):c.499G>A (p.Gly167Arg)

Gene:

MPZ:myelin protein zero [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q23.3

Genomic location:

Preferred name:

NM_000530.8(MPZ):c.499G>A (p.Gly167Arg)

HGVS:

NC_000001.11:g.161306414C>T
NG_008055.1:g.8559G>A
NM_000530.8:c.499G>AMANE SELECT
NM_001315491.2:c.499G>A
NP_000521.2:p.Gly167Arg
NP_001302420.1:p.Gly167Arg
LRG_256t1:c.499G>A
LRG_256:g.8559G>A
LRG_256p1:p.Gly167Arg
NC_000001.10:g.161276204C>T
NM_000530.6:c.499G>A
P25189:p.Gly167Arg

Protein change:

G167R

Links:

UniProtKB: P25189#VAR_004544; dbSNP: rs121913586

Molecular consequence:

NM_000530.8:c.499G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001315491.2:c.499G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Charcot-Marie-Tooth disease, type I (CMT1)
Synonyms:: Charcot-Marie-Tooth, Type 1; Charcot-Marie-Tooth disease type 1
Identifiers:: MONDO: MONDO:0019011; MedGen: C0751036

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001217864	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 24, 2021)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 7506095, 10399750, 12242557, 29687021, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001217864

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 24, 2021)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

De novo mutation of the myelin P0 gene in Dejerine-Sottas disease (hereditary motor and sensory neuropathy type III).

Hayasaka K, Himoro M, Sawaishi Y, Nanao K, Takahashi T, Takada G, Nicholson GA, Ouvrier RA, Tachi N.

Nat Genet. 1993 Nov;5(3):266-8.

PubMed [citation]

PMID:: 7506095

Germline mosaicism of MPZ gene in Dejerine-Sottas syndrome (HMSN III) associated with hereditary stomatocytosis.

Takashima H, Nakagawa M, Kanzaki A, Yawata Y, Horikiri T, Matsuzaki T, Suehara M, Izumo S, Osame M.

Neuromuscul Disord. 1999 Jun;9(4):232-8.

PubMed [citation]

PMID:: 10399750

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001217864.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 167 of the MPZ protein (p.Gly167Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Dejerine-Sottas disease (PMID: 7506095, 10399750, 12242557). In at least one individual the variant was observed to be de novo. This variant is also known as p.Gly138Arg. ClinVar contains an entry for this variant (Variation ID: 208149). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Experimental studies have shown that this missense change affects MPZ function (PMID: 29687021). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 4, 2026

ClinVar

Relating variation to medicine