NM_000530.8(MPZ):c.418T>A (p.Ser140Thr) AND MPZ-related polyneuropathy

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 23, 2025
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:: RCV006646127.2

Allele description [Variation Report for NM_000530.8(MPZ):c.418T>A (p.Ser140Thr)]

NM_000530.8(MPZ):c.418T>A (p.Ser140Thr)

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.418T>A (p.Ser140Thr)

HGVS:

NC_000001.11:g.161306738A>T
NG_008055.1:g.8235T>A
NM_000530.8:c.418T>AMANE SELECT
NM_001315491.2:c.418T>A
NP_000521.2:p.Ser140Thr
NP_001302420.1:p.Ser140Thr
LRG_256t1:c.418T>A
LRG_256:g.8235T>A
NC_000001.10:g.161276528A>T
NM_000530.6:c.418T>A

Protein change:

S140T

Links:

dbSNP: rs572010627

Molecular consequence:

NM_000530.8:c.418T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001315491.2:c.418T>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: MPZ-related polyneuropathy
Identifiers:

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV007539068	Clinical Genetics Laboratory, Region Ostergotland	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 23, 2025)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 26310628, 12207932, 14711881, 37273706, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV007539068

Clinical Genetics Laboratory, Region Ostergotland

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 23, 2025)

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genotype-phenotype characteristics and baseline natural history of heritable neuropathies caused by mutations in the MPZ gene.

Sanmaneechai O, Feely S, Scherer SS, Herrmann DN, Burns J, Muntoni F, Li J, Siskind CE, Day JW, Laura M, Sumner CJ, Lloyd TE, Ramchandren S, Shy RR, Grider T, Bacon C, Finkel RS, Yum SW, Moroni I, Piscosquito G, Pareyson D, Reilly MM, et al.

Brain. 2015 Nov;138(Pt 11):3180-92. doi: 10.1093/brain/awv241. Epub 2015 Aug 25.

PubMed [citation]

PMID:: 26310628
PMCID:: PMC4643641

Charcot-Marie-Tooth neuropathy: clinical phenotypes of four novel mutations in the MPZ and Cx 32 genes.

Street VA, Meekins G, Lipe HP, Seltzer WK, Carter GT, Kraft GH, Bird TD.

Neuromuscul Disord. 2002 Oct;12(7-8):643-50.

PubMed [citation]

PMID:: 12207932

See all PubMed Citations (5)

Details of each submission

From Clinical Genetics Laboratory, Region Ostergotland, SCV007539068.2

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

Description

The NM_000530.8:c.418T>A missense variant (REVEL score = 0.692) is rare in population database (0.00047% gnomAD-nonUKB v4.1.0) and is located in a cluster of amino acids in the MPZ ex- tracellular domain where substitutions are reported as disease causing (PMID:26310628). The variant cosegregates with disease in multiple affected family members and the prevalence of the variant in affected individuals is significantly increased compared with controls (PMID:12207932, PMID:14711881, PMID: 37273706 and in-house data). The following ACMG/AMP criteria were applied in classifying this variant: PM1, PM2, PP1_strong, PP3, PS4_moderate

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

Last Updated: Sep 27, 2026

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