NM_000530.8(MPZ):c.59C>T (p.Ser20Phe) AND Charcot-Marie-Tooth disease, type I

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 13, 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:: RCV002536916.3

Allele description [Variation Report for NM_000530.8(MPZ):c.59C>T (p.Ser20Phe)]

NM_000530.8(MPZ):c.59C>T (p.Ser20Phe)

Genes:

SDHC:succinate dehydrogenase complex subunit C [Gene - OMIM - HGNC]
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.59C>T (p.Ser20Phe)

HGVS:

NC_000001.11:g.161309847G>A
NG_008055.1:g.5126C>T
NG_012767.1:g.472G>A
NM_000530.8:c.59C>TMANE SELECT
NM_001315491.2:c.59C>T
NP_000521.2:p.Ser20Phe
NP_001302420.1:p.Ser20Phe
LRG_256t1:c.59C>T
LRG_256:g.5126C>T
LRG_317:g.472G>A
NC_000001.10:g.161279637G>A
NM_000530.6:c.59C>T

Protein change:

S20F

Links:

dbSNP: rs932826788

NCBI 1000 Genomes Browser:

rs932826788

Molecular consequence:

NM_000530.8:c.59C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001315491.2:c.59C>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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003492332	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 13, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16987171, 34008892, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003492332

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 13, 2023)

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

Novel C59T leader peptide mutation in the MPZ gene associated with late-onset, axonal, sensorimotor polyneuropathy.

Finsterer J, Miltenberger G, Rauschka H, Janecke A.

Eur J Neurol. 2006 Oct;13(10):1149-52.

PubMed [citation]

PMID:: 16987171

Phenotype-driven variant filtration strategy in exome sequencing toward a high diagnostic yield and identification of 85 novel variants in 400 patients with rare Mendelian disorders.

Marinakis NM, Svingou M, Veltra D, Kekou K, Sofocleous C, Tilemis FN, Kosma K, Tsoutsou E, Fryssira H, Traeger-Synodinos J.

Am J Med Genet A. 2021 Aug;185(8):2561-2571. doi: 10.1002/ajmg.a.62338. Epub 2021 May 19.

PubMed [citation]

PMID:: 34008892

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003492332.2

#	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 serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 20 of the MPZ protein (p.Ser20Phe). This variant is present in population databases (no rsID available, gnomAD 0.001%). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 16987171, 34008892). ClinVar contains an entry for this variant (Variation ID: 637322). 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. 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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