NM_000530.8(MPZ):c.263A>G (p.Tyr88Cys) AND Charcot-Marie-Tooth disease, type I

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 15, 2017
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:: RCV000638158.2

Allele description [Variation Report for NM_000530.8(MPZ):c.263A>G (p.Tyr88Cys)]

NM_000530.8(MPZ):c.263A>G (p.Tyr88Cys)

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.263A>G (p.Tyr88Cys)

HGVS:

NC_000001.11:g.161306893T>C
NG_008055.1:g.8080A>G
NM_000530.8:c.263A>GMANE SELECT
NM_001315491.2:c.263A>G
NP_000521.2:p.Tyr88Cys
NP_001302420.1:p.Tyr88Cys
LRG_256t1:c.263A>G
LRG_256:g.8080A>G
NC_000001.10:g.161276683T>C
NM_000530.6:c.263A>G

Protein change:

Y88C

Links:

dbSNP: rs1553259700

NCBI 1000 Genomes Browser:

rs1553259700

Molecular consequence:

NM_000530.8:c.263A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001315491.2:c.263A>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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000759644	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 15, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 27025386, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000759644

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 15, 2017)

germline

clinical testing

PubMed (2)
[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

Identification of Genetic Causes of Inherited Peripheral Neuropathies by Targeted Gene Panel Sequencing.

Nam SH, Hong YB, Hyun YS, Nam da E, Kwak G, Hwang SH, Choi BO, Chung KW.

Mol Cells. 2016 May 31;39(5):382-8. doi: 10.14348/molcells.2016.2288. Epub 2016 Mar 30.

PubMed [citation]

PMID:: 27025386
PMCID:: PMC4870185

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000759644.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces tyrosine with cysteine at codon 88 of the MPZ protein (p.Tyr88Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). A different missense substitution at this codon (p.Tyr88His) has been reported in an individual affected with Charcot-Marie-Tooth disease (PMID: 27025386). 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"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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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