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NM_000530.8(MPZ):c.244T>C (p.Tyr82His) AND Charcot-Marie-Tooth disease, type I

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 24, 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:
RCV000693764.15

Allele description [Variation Report for NM_000530.8(MPZ):c.244T>C (p.Tyr82His)]

NM_000530.8(MPZ):c.244T>C (p.Tyr82His)

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.244T>C (p.Tyr82His)
HGVS:
  • NC_000001.11:g.161306912A>G
  • NG_008055.1:g.8061T>C
  • NM_000530.8:c.244T>CMANE SELECT
  • NM_001315491.2:c.244T>C
  • NP_000521.2:p.Tyr82His
  • NP_000521.2:p.Tyr82His
  • NP_001302420.1:p.Tyr82His
  • LRG_256t1:c.244T>C
  • LRG_256:g.8061T>C
  • LRG_256p1:p.Tyr82His
  • NC_000001.10:g.161276702A>G
  • NM_000530.5:c.274T>C
  • NM_000530.6:c.244T>C
Protein change:
Y82H
Links:
dbSNP: rs281865124
NCBI 1000 Genomes Browser:
rs281865124
Molecular consequence:
  • NM_000530.8:c.244T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001315491.2:c.244T>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
SCV000821645Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jan 24, 2023) 		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

Late onset axonal Charcot-Marie-Tooth phenotype caused by a novel myelin protein zero mutation.

Bienfait HM, Faber CG, Baas F, Gabreëls-Festen AA, Koelman JH, Hoogendijk JE, Verschuuren JJ, Wokke JH, de Visser M.

J Neurol Neurosurg Psychiatry. 2006 Apr;77(4):534-7.

PubMed [citation]
PMID:
16543539
PMCID:
PMC2077493

New mutation of the myelin P0 gene in a pedigree of Charcot-Marie-Tooth neuropathy 1.

Himoro M, Yoshikawa H, Matsui T, Mitsui Y, Takahashi M, Kaido M, Nishimura T, Sawaishi Y, Takada G, Hayasaka K.

Biochem Mol Biol Int. 1993 Sep;31(1):169-73.

PubMed [citation]
PMID:
7505151
See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000821645.4

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

Description

This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 82 of the MPZ protein (p.Tyr82His). This missense change has been observed in individual(s) with late onset axonal Charcot-Marie-Tooth disease (PMID: 16543539). It has also been observed to segregate with disease in related individuals. For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Tyr82 amino acid residue in MPZ. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7505151, 9633821, 12402337, 25429913). 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 41017).

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

Last Updated: Nov 10, 2024