NM_000530.8(MPZ):c.670G>T (p.Asp224Tyr) AND Charcot-Marie-Tooth disease, type I

Clinical significance:Pathogenic (Last evaluated: Apr 24, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000700463.1

Allele description [Variation Report for NM_000530.8(MPZ):c.670G>T (p.Asp224Tyr)]

NM_000530.8(MPZ):c.670G>T (p.Asp224Tyr)

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.670G>T (p.Asp224Tyr)
HGVS:
  • NC_000001.11:g.161305953C>A
  • NG_008055.1:g.9020G>T
  • NM_000530.8:c.670G>TMANE SELECT
  • NM_001315491.2:c.670G>T
  • NP_000521.2:p.Asp224Tyr
  • NP_001302420.1:p.Asp224Tyr
  • LRG_256t1:c.670G>T
  • LRG_256:g.9020G>T
  • LRG_256p1:p.Asp224Tyr
  • NC_000001.10:g.161275743C>A
  • NM_000530.5:c.700G>T
  • NM_000530.6:c.670G>T
  • P25189:p.Asp224Tyr
Protein change:
D224Y
Links:
UniProtKB: P25189#VAR_054397; dbSNP: rs267607247
NCBI 1000 Genomes Browser:
rs267607247
Molecular consequence:
  • NM_000530.8:c.670G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001315491.2:c.670G>T - 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
SCV000829220Invitaecriteria provided, single submitter
Pathogenic
(Apr 24, 2018)
germlineclinical testing

PubMed (6)
[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

Unusual Charcot-Marie-Tooth phenotype due to a mutation within the intracellular domain of myelin protein zero.

Schneider-Gold C, Kötting J, Epplen JT, Gold R, Gerding WM.

Muscle Nerve. 2010 Apr;41(4):550-4. doi: 10.1002/mus.21523.

PubMed [citation]
PMID:
19882637

Analyzing histopathological features of rare charcot-marie-tooth neuropathies to unravel their pathogenesis.

Benedetti S, Previtali SC, Coviello S, Scarlato M, Cerri F, Di Pierri E, Piantoni L, Spiga I, Fazio R, Riva N, Natali Sora MG, Dacci P, Malaguti MC, Munerati E, Grimaldi LM, Marrosu MG, De Pellegrin M, Ferrari M, Comi G, Quattrini A, Bolino A.

Arch Neurol. 2010 Dec;67(12):1498-505. doi: 10.1001/archneurol.2010.303.

PubMed [citation]
PMID:
21149811
See all PubMed Citations (6)

Details of each submission

From Invitae, SCV000829220.1

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

Description

This sequence change replaces aspartic acid with tyrosine at codon 224 of the MPZ protein (p.Asp224Tyr). The aspartic acid residue is highly conserved and there is a large physicochemical difference between aspartic acid and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in a family segregating with disease (PMID: 19882637) and in multiple unrelated individuals affected with Charcot-Marie-Tooth disease (CMT) (PMID:21149811, 19259128, 27088055). This variant has also been reported as homozygous in a family with CMT type 1B (PMID:16488608). ClinVar contains an entry for this variant (Variation ID: 41024). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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: Nov 27, 2021

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