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NM_000530.8(MPZ):c.389A>G (p.Lys130Arg) AND Charcot-Marie-Tooth disease, type I

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 22, 2023
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:
RCV000819474.15

Allele description [Variation Report for NM_000530.8(MPZ):c.389A>G (p.Lys130Arg)]

NM_000530.8(MPZ):c.389A>G (p.Lys130Arg)

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.389A>G (p.Lys130Arg)
HGVS:
  • NC_000001.11:g.161306767T>C
  • NG_008055.1:g.8206A>G
  • NM_000530.8:c.389A>GMANE SELECT
  • NM_001315491.2:c.389A>G
  • NP_000521.2:p.Lys130Arg
  • NP_001302420.1:p.Lys130Arg
  • LRG_256t1:c.389A>G
  • LRG_256:g.8206A>G
  • LRG_256p1:p.Lys130Arg
  • NC_000001.10:g.161276557T>C
  • NM_000530.5:c.419A>G
  • NM_000530.6:c.389A>G
  • P25189:p.Lys130Arg
Protein change:
K130R
Links:
UniProtKB: P25189#VAR_004534; dbSNP: rs281865127
NCBI 1000 Genomes Browser:
rs281865127
Molecular consequence:
  • NM_000530.8:c.389A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001315491.2:c.389A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000960137Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Nov 22, 2023) 		germlineclinical testing

PubMed (8)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A new mutation of the Po gene in patients with Charcot-Marie-Tooth disease type 1B: screening of the Po gene by heteroduplex analysis.

Tachi N, Kozuka N, Ohya K, Chiba S, Sasaki K, Uyemura K, Hayasaka K.

Neurosci Lett. 1996 Feb 9;204(3):173-6.

PubMed [citation]
PMID:
8938258

Mutations in the peripheral myelin protein zero and connexin32 genes detected by non-isotopic RNase cleavage assay and their phenotypes in Japanese patients with Charcot-Marie-Tooth disease.

Yoshihara T, Yamamoto M, Doyu M, Mis KI, Hattori N, Hasegawa Y, Mokuno K, Mitsuma T, Sobue G.

Hum Mutat. 2000 Aug;16(2):177-8.

PubMed [citation]
PMID:
10923043
See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000960137.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)

Description

This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 130 of the MPZ protein (p.Lys130Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease type 1B and/or Dejerine-Sottas syndrome (PMID: 8938258, 10923043, 12090401, 26454100, 27353517, 29670817). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 41021). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MPZ protein function with a negative predictive value of 80%. Studies have shown that this missense change alters MPZ gene expression (PMID: 11182278). For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 26, 2024