NM_000530.8(MPZ):c.316C>T (p.Arg106Cys) AND Charcot-Marie-Tooth disease, type I

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 4, 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:: RCV001061577.6

Allele description [Variation Report for NM_000530.8(MPZ):c.316C>T (p.Arg106Cys)]

NM_000530.8(MPZ):c.316C>T (p.Arg106Cys)

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.316C>T (p.Arg106Cys)

HGVS:

NC_000001.11:g.161306840G>A
NG_008055.1:g.8133C>T
NM_000530.8:c.316C>TMANE SELECT
NM_001315491.2:c.316C>T
NP_000521.2:p.Arg106Cys
NP_001302420.1:p.Arg106Cys
LRG_256t1:c.316C>T
LRG_256:g.8133C>T
NC_000001.10:g.161276630G>A
NM_000530.6:c.316C>T

Protein change:

R106C

Links:

dbSNP: rs1571819084

NCBI 1000 Genomes Browser:

rs1571819084

Molecular consequence:

NM_000530.8:c.316C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001315491.2:c.316C>T - 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

Recent activity

Clear Turn Off Turn On

Homo sapiens procollagen-lysine,2-oxoglutarate 5-dioxygenase 1 (PLOD1), transcri...
Homo sapiens procollagen-lysine,2-oxoglutarate 5-dioxygenase 1 (PLOD1), transcript variant 2, mRNA
gi|1519244798|ref|NM_000302.4|

Nucleotide
uncharacterized protein YALI1_D26610g [Yarrowia lipolytica]
uncharacterized protein YALI1_D26610g [Yarrowia lipolytica]
gi|50551245|ref|XP_503096.1|

Protein
Homo sapiens polyribonucleotide nucleotidyltransferase 1 (PNPT1), mRNA
Homo sapiens polyribonucleotide nucleotidyltransferase 1 (PNPT1), mRNA
gi|188528627|ref|NM_033109.3|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001226325	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 4, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 22222859, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001226325

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 4, 2023)

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

A novel mutation of myelin protein zero associated with late-onset predominantly axonal Charcot-Marie-Tooth disease.

Marttila M, Rautenstrauss B, Huehne K, Laitinen V, Majamaa K, Kärppä M.

J Neurol. 2012 Aug;259(8):1585-9. doi: 10.1007/s00415-011-6382-5. Epub 2012 Jan 6.

PubMed [citation]

PMID:: 22222859

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, SCV001226325.5

#	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 arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 106 of the MPZ protein (p.Arg106Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with Charcot-Marie-Tooth disease (PMID: 22222859). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 637797). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MPZ protein function with a negative predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.

#	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

ClinVar

Relating variation to medicine