NM_000530.8(MPZ):c.397C>A (p.Pro133Thr) AND Charcot-Marie-Tooth disease, type I

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 5, 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:: RCV000525895.9

Allele description [Variation Report for NM_000530.8(MPZ):c.397C>A (p.Pro133Thr)]

NM_000530.8(MPZ):c.397C>A (p.Pro133Thr)

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.397C>A (p.Pro133Thr)

HGVS:

NC_000001.11:g.161306759G>T
NG_008055.1:g.8214C>A
NM_000530.8:c.397C>AMANE SELECT
NM_001315491.2:c.397C>A
NP_000521.2:p.Pro133Thr
NP_001302420.1:p.Pro133Thr
LRG_256t1:c.397C>A
LRG_256:g.8214C>A
NC_000001.10:g.161276549G>T
NM_000530.6:c.397C>A

Protein change:

P133T

Links:

dbSNP: rs1553259648

NCBI 1000 Genomes Browser:

rs1553259648

Molecular consequence:

NM_000530.8:c.397C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001315491.2:c.397C>A - 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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PREDICTED: patatin-like phospholipase domain-containing protein 4 [Haliaeetus le...
PREDICTED: patatin-like phospholipase domain-containing protein 4 [Haliaeetus leucocephalus]
gi|729765569|ref|XP_010579893.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000636249	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 5, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22433810, 26310628, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000636249

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 5, 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

[Clinical-genetic correlations in the hereditary motor-sensor neuropathy caused by mutations in the MPZ (P0) gene].

Milovidova TB, Dadali EL, Fedotov VP, Shchagina OA, Poliakov AV.

Zh Nevrol Psikhiatr Im S S Korsakova. 2011;111(12):48-55. Russian.

PubMed [citation]

PMID:: 22433810

Genotype-phenotype characteristics and baseline natural history of heritable neuropathies caused by mutations in the MPZ gene.

Sanmaneechai O, Feely S, Scherer SS, Herrmann DN, Burns J, Muntoni F, Li J, Siskind CE, Day JW, Laura M, Sumner CJ, Lloyd TE, Ramchandren S, Shy RR, Grider T, Bacon C, Finkel RS, Yum SW, Moroni I, Piscosquito G, Pareyson D, Reilly MM, et al.

Brain. 2015 Nov;138(Pt 11):3180-92. doi: 10.1093/brain/awv241. Epub 2015 Aug 25.

PubMed [citation]

PMID:: 26310628
PMCID:: PMC4643641

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000636249.6

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

Description

This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 133 of the MPZ protein (p.Pro133Thr). This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Pro133 amino acid residue in MPZ. Other variant(s) that disrupt this residue have been observed in individuals with MPZ-related conditions (PMID: 22433810, 26310628), which suggests that this may be a clinically significant amino acid residue. 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. ClinVar contains an entry for this variant (Variation ID: 462797). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease (Invitae). In at least one individual the variant was observed to be de novo.

#	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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