NM_000530.8(MPZ):c.245A>C (p.Tyr82Ser) AND Charcot-Marie-Tooth disease, type I

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 30, 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:: RCV003581727.1

Allele description

NM_000530.8(MPZ):c.245A>C (p.Tyr82Ser)

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>C (p.Tyr82Ser)

HGVS:

NC_000001.11:g.161306911T>G
NG_008055.1:g.8062A>C
NM_000530.8:c.245A>CMANE SELECT
NM_001315491.2:c.245A>C
NP_000521.2:p.Tyr82Ser
NP_001302420.1:p.Tyr82Ser
LRG_256t1:c.245A>C
LRG_256:g.8062A>C
NC_000001.10:g.161276701T>G
NM_000530.6:c.245A>C

Protein change:

Y82S

Links:

dbSNP: rs1553259707

NCBI 1000 Genomes Browser:

rs1553259707

Molecular consequence:

NM_000530.8:c.245A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001315491.2:c.245A>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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004293778	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 30, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25429913, 16543539, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004293778

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 30, 2022)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Charcot-Marie-Tooth disease: frequency of genetic subtypes in a Southern Italy population.

Manganelli F, Tozza S, Pisciotta C, Bellone E, Iodice R, Nolano M, Geroldi A, Capponi S, Mandich P, Santoro L.

J Peripher Nerv Syst. 2014 Dec;19(4):292-8. doi: 10.1111/jns.12092.

PubMed [citation]

PMID:: 25429913

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

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV004293778.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

ClinVar contains an entry for this variant (Variation ID: 637783). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 25429913). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with serine, which is neutral and polar, at codon 82 of the MPZ protein (p.Tyr82Ser). 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. 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: 16543539). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 20, 2024

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