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NM_000530.8(MPZ):c.245A>G (p.Tyr82Cys) AND Charcot-Marie-Tooth disease, type I

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 12, 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:
RCV000701835.10

Allele description [Variation Report for NM_000530.8(MPZ):c.245A>G (p.Tyr82Cys)]

NM_000530.8(MPZ):c.245A>G (p.Tyr82Cys)

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.245A>G (p.Tyr82Cys)
HGVS:
  • NC_000001.11:g.161306911T>C
  • NG_008055.1:g.8062A>G
  • NM_000530.8:c.245A>GMANE SELECT
  • NM_001315491.2:c.245A>G
  • NP_000521.2:p.Tyr82Cys
  • NP_001302420.1:p.Tyr82Cys
  • LRG_256t1:c.245A>G
  • LRG_256:g.8062A>G
  • NC_000001.10:g.161276701T>C
  • NM_000530.6:c.245A>G
  • NM_000530.7:c.245A>G
Protein change:
Y82C
Links:
dbSNP: rs1553259707
NCBI 1000 Genomes Browser:
rs1553259707
Molecular consequence:
  • NM_000530.8:c.245A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001315491.2:c.245A>G - 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
SCV000830654Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(May 12, 2022) 		germlineclinical testing

PubMed (7)
[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

Spectrum of mutations in Finnish patients with Charcot-Marie-Tooth disease and related neuropathies.

Silander K, Meretoja P, Juvonen V, Ignatius J, Pihko H, Saarinen A, Wallden T, Herrgård E, Aula P, Savontaus ML.

Hum Mutat. 1998;12(1):59-68.

PubMed [citation]
PMID:
9633821

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 (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000830654.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 82 of the MPZ protein (p.Tyr82Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Charcot-Marie-Tooth (CMT) disease type 1 and Déjérine-Sottas syndrome (PMID: 7505151, 9633821, 11545686, 11835375, 12402337, 26310628). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 549681). 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. 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, 11545686, 11835375, 12402337, 26310628). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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: Sep 29, 2024