U.S. flag

An official website of the United States government

NM_000530.8(MPZ):c.268G>A (p.Asp90Asn) AND Charcot-Marie-Tooth disease, type I

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Aug 9, 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:
RCV000705483.7

Allele description [Variation Report for NM_000530.8(MPZ):c.268G>A (p.Asp90Asn)]

NM_000530.8(MPZ):c.268G>A (p.Asp90Asn)

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.268G>A (p.Asp90Asn)
HGVS:
  • NC_000001.11:g.161306888C>T
  • NG_008055.1:g.8085G>A
  • NM_000530.8:c.268G>AMANE SELECT
  • NM_001315491.2:c.268G>A
  • NP_000521.2:p.Asp90Asn
  • NP_001302420.1:p.Asp90Asn
  • LRG_256t1:c.268G>A
  • LRG_256:g.8085G>A
  • NC_000001.10:g.161276678C>T
  • NM_000530.6:c.268G>A
Protein change:
D90N
Links:
dbSNP: rs1558154208
NCBI 1000 Genomes Browser:
rs1558154208
Molecular consequence:
  • NM_000530.8:c.268G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001315491.2:c.268G>A - 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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000834482Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Aug 9, 2022) 		germlineclinical testing

PubMed (4)
[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

Charcot-Marie-Tooth neuropathy type 1B is associated with mutations of the myelin P0 gene.

Hayasaka K, Himoro M, Sato W, Takada G, Uyemura K, Shimizu N, Bird TD, Conneally PM, Chance PF.

Nat Genet. 1993 Sep;5(1):31-4.

PubMed [citation]
PMID:
7693129

Charcot-Marie-Tooth disease in Cyprus: epidemiological, clinical and genetic characteristics.

Nicolaou P, Zamba-Papanicolaou E, Koutsou P, Kleopa KA, Georghiou A, Hadjigeorgiou G, Papadimitriou A, Kyriakides T, Christodoulou K.

Neuroepidemiology. 2010;35(3):171-7. doi: 10.1159/000314351. Epub 2010 Jun 23.

PubMed [citation]
PMID:
20571287
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000834482.4

#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.Asp90 amino acid residue in MPZ. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7693129, 20571287, 25694466). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 581604). This variant has not been reported in the literature in individuals affected with MPZ-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 90 of the MPZ protein (p.Asp90Asn).

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

Last Updated: Sep 29, 2024