U.S. flag

An official website of the United States government

NM_000530.8(MPZ):c.181G>A (p.Asp61Asn) AND Charcot-Marie-Tooth disease, type I

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 10, 2019
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:
RCV000688094.17

Allele description [Variation Report for NM_000530.8(MPZ):c.181G>A (p.Asp61Asn)]

NM_000530.8(MPZ):c.181G>A (p.Asp61Asn)

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.181G>A (p.Asp61Asn)
HGVS:
  • NC_000001.11:g.161307311C>T
  • NG_008055.1:g.7662G>A
  • NM_000530.8:c.181G>AMANE SELECT
  • NM_001315491.2:c.181G>A
  • NP_000521.2:p.Asp61Asn
  • NP_001302420.1:p.Asp61Asn
  • LRG_256t1:c.181G>A
  • LRG_256:g.7662G>A
  • LRG_256p1:p.Asp61Asn
  • NC_000001.10:g.161277101C>T
  • NM_000530.6:c.181G>A
Protein change:
D61N
Links:
dbSNP: rs797044845
NCBI 1000 Genomes Browser:
rs797044845
Molecular consequence:
  • NM_000530.8:c.181G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001315491.2:c.181G>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
SCV000815692Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(May 10, 2019) 		germlineclinical testing

PubMed (5)
[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 2 and P0 point mutations: two novel amino acid substitutions (Asp61Gly; Tyr119Cys) and a possible "hotspot" on Thr124Met.

Senderek J, Hermanns B, Lehmann U, Bergmann C, Marx G, Kabus C, Timmerman V, Stoltenburg-Didinger G, Schröder JM.

Brain Pathol. 2000 Apr;10(2):235-48.

PubMed [citation]
PMID:
10764043
PMCID:
PMC8098375

Congenital hypomyelinating neuropathy attributable to a de novo p.Asp61Asn mutation of the myelin protein zero gene.

Yonekawa T, Komaki H, Saito Y, Takashima H, Sasaki M.

Pediatr Neurol. 2013 Jan;48(1):59-62. doi: 10.1016/j.pediatrneurol.2012.09.011.

PubMed [citation]
PMID:
23290023
See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000815692.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change replaces aspartic acid with asparagine at codon 61 of the MPZ protein (p.Asp61Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. A different missense substitution at this codon (p.Asp61Gly) has been determined to be pathogenic (PMID: 10764043). This suggests that the aspartic acid residue is critical for MPZ protein function and that other missense substitutions at this position may also be pathogenic. Experimental studies have shown that this missense change results in increased glycosylation of the MPZ protein and impairs intracellular trafficking (PMID: 22451207). This variant has been reported to be de novo in an individual affected with congenital hypomyelinating neuropathy (PMID: 23290023). This variant has also been reported in individuals affected with Charcot-Marie-Tooth disease (PMID: 22451207, 11484669). ClinVar contains an entry for this variant (Variation ID: 208146).

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

Last Updated: Oct 26, 2024