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NM_000530.8(MPZ):c.186C>G (p.Ile62Met) AND Charcot-Marie-Tooth disease, type I

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Aug 17, 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:
RCV000799870.4

Allele description

NM_000530.8(MPZ):c.186C>G (p.Ile62Met)

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.186C>G (p.Ile62Met)
HGVS:
  • NC_000001.11:g.161307306G>C
  • NG_008055.1:g.7667C>G
  • NM_000530.8:c.186C>GMANE SELECT
  • NM_001315491.2:c.186C>G
  • NP_000521.2:p.Ile62Met
  • NP_001302420.1:p.Ile62Met
  • LRG_256t1:c.186C>G
  • LRG_256:g.7667C>G
  • LRG_256p1:p.Ile62Met
  • NC_000001.10:g.161277096G>C
  • NM_000530.6:c.186C>G
  • P25189:p.Ile62Met
Protein change:
I62M; ILE62MET
Links:
UniProtKB: P25189#VAR_029973; OMIM: 159440.0029; dbSNP: rs121913605
NCBI 1000 Genomes Browser:
rs121913605
Molecular consequence:
  • NM_000530.8:c.186C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001315491.2:c.186C>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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000939552Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Aug 17, 2023)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

A novel MPZ gene mutation in dominantly inherited neuropathy with focally folded myelin sheaths.

Nakagawa M, Suehara M, Saito A, Takashima H, Umehara F, Saito M, Kanzato N, Matsuzaki T, Takenaga S, Sakoda S, Izumo S, Osame M.

Neurology. 1999 Apr 12;52(6):1271-5.

PubMed [citation]
PMID:
10214757

Altered trafficking and adhesion function of MPZ mutations and phenotypes of Charcot-Marie-Tooth disease 1B.

Matsuyama W, Nakagawa M, Takashima H, Osame M.

Acta Neuropathol. 2002 May;103(5):501-8. Epub 2002 Jan 31.

PubMed [citation]
PMID:
11935267
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000939552.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Ile62 amino acid residue in MPZ. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10214757, 11935267). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. ClinVar contains an entry for this variant (Variation ID: 14194). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 14638973). This variant is present in population databases (rs121913605, gnomAD 0.003%). This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 62 of the MPZ protein (p.Ile62Met).

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

Last Updated: Jul 23, 2024