NM_000530.8(MPZ):c.368_369delinsCT (p.Gly123Ala) AND Charcot-Marie-Tooth disease, type I

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 21, 2016
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:: RCV000231316.6

Allele description [Variation Report for NM_000530.8(MPZ):c.368_369delinsCT (p.Gly123Ala)]

NM_000530.8(MPZ):c.368_369delinsCT (p.Gly123Ala)

Gene:

MPZ:myelin protein zero [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

1q23.3

Genomic location:

Preferred name:

NM_000530.8(MPZ):c.368_369delinsCT (p.Gly123Ala)

HGVS:

NC_000001.11:g.161306787_161306788delinsAG
NG_008055.1:g.8185_8186delinsCT
NM_000530.8:c.368_369delinsCTMANE SELECT
NM_001315491.2:c.368_369delinsCT
NP_000521.2:p.Gly123Ala
NP_001302420.1:p.Gly123Ala
LRG_256t1:c.368_369delGCinsCT
LRG_256:g.8185_8186delinsCT
NC_000001.10:g.161276577_161276578delinsAG
NM_000530.6:c.368_369delGCinsCT

Protein change:

G123A

Links:

dbSNP: rs878854030

NCBI 1000 Genomes Browser:

rs878854030

Molecular consequence:

NM_000530.8:c.368_369delinsCT - missense variant - [Sequence Ontology: SO:0001583]
NM_001315491.2:c.368_369delinsCT - 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
SCV000285037	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 21, 2016)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 24053775, 18209201, 20385006, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000285037

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 21, 2016)

germline

clinical testing

PubMed (4)
[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

Diagnostic laboratory testing for Charcot Marie Tooth disease (CMT): the spectrum of gene defects in Norwegian patients with CMT and its implications for future genetic test strategies.

Østern R, Fagerheim T, Hjellnes H, Nygård B, Mellgren SI, Nilssen Ø.

BMC Med Genet. 2013 Sep 21;14:94. doi: 10.1186/1471-2350-14-94.

PubMed [citation]

PMID:: 24053775
PMCID:: PMC3849068

MPZ mutation G123S characterization: evidence for a complex pathogenesis in CMT disease.

Lee YC, Yu CT, Lin KP, Chang MH, Hsu SL, Liu YF, Lu YC, Soong BW.

Neurology. 2008 Jan 22;70(4):273-7. doi: 10.1212/01.wnl.0000296828.66915.bf.

PubMed [citation]

PMID:: 18209201

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000285037.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change deletes 2 nucleotides and inserts 2 different nucleotides in exon 3 of the MPZ mRNA (c.368_369delGCinsCT). This results in a substitution of glycine at codon 123 with alanine. In summary, this is a novel missense change and although multiple missense variants have been reported at this codon in individuals with CMT, in the absence of additional functional data and/or segregation data, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (PolyPhen-2, Align-GVGD) suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a MPZ-related disease. However, multiple other missense variants have been reported at codon 123 in individuals with Charcot-Marie-Tooth (CMT) disease (PMID: 24053775, 18209201, 20385006) and in other codons in the surrounding region suggesting that this codon as well as the surrounding region are likely important for MPZ protein function.

#	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: Sep 29, 2024

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