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NM_000530.8(MPZ):c.331T>C (p.Ser111Pro) AND Charcot-Marie-Tooth disease, type I

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jul 19, 2022
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:
RCV000549580.8

Allele description [Variation Report for NM_000530.8(MPZ):c.331T>C (p.Ser111Pro)]

NM_000530.8(MPZ):c.331T>C (p.Ser111Pro)

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.331T>C (p.Ser111Pro)
HGVS:
  • NC_000001.11:g.161306825A>G
  • NG_008055.1:g.8148T>C
  • NM_000530.8:c.331T>CMANE SELECT
  • NM_001315491.2:c.331T>C
  • NP_000521.2:p.Ser111Pro
  • NP_001302420.1:p.Ser111Pro
  • LRG_256t1:c.331T>C
  • LRG_256:g.8148T>C
  • NC_000001.10:g.161276615A>G
  • NM_000530.6:c.331T>C
Protein change:
S111P
Links:
dbSNP: rs1553259664
NCBI 1000 Genomes Browser:
rs1553259664
Molecular consequence:
  • NM_000530.8:c.331T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001315491.2:c.331T>C - 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
SCV000636245Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jul 19, 2022) 		germlineclinical testing

PubMed (6)
[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

Genetic spectrum of Charcot-Marie-Tooth disease associated with myelin protein zero gene variants in Japan.

Taniguchi T, Ando M, Okamoto Y, Yoshimura A, Higuchi Y, Hashiguchi A, Shiga K, Hayashida A, Hatano T, Ishiura H, Mitsui J, Hattori N, Mizuno T, Nakagawa M, Tsuji S, Takashima H.

Clin Genet. 2021 Mar;99(3):359-375. doi: 10.1111/cge.13881. Epub 2020 Nov 27.

PubMed [citation]
PMID:
33179255
PMCID:
PMC7898366

Myelin protein zero mutations and the unfolded protein response in Charcot Marie Tooth disease type 1B.

Bai Y, Wu X, Brennan KM, Wang DS, D'Antonio M, Moran J, Svaren J, Shy ME.

Ann Clin Transl Neurol. 2018 Apr;5(4):445-455. doi: 10.1002/acn3.543.

PubMed [citation]
PMID:
29687021
PMCID:
PMC5899917
See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000636245.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This missense change has been observed in individual(s) with Charcot–Marie–Tooth disease type 1B (CMT1B) and/or inherited peripheral neuropathy (PMID: 26310628, 33179255). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 111 of the MPZ protein (p.Ser111Pro). ClinVar contains an entry for this variant (Variation ID: 462794). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects MPZ function (PMID: 29687021). This variant disrupts the p.Ser111 amino acid residue in MPZ. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 19293842, 25429913, 26310628). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.

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

Last Updated: Sep 29, 2024