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NM_000530.8(MPZ):c.409G>A (p.Gly137Ser) AND Charcot-Marie-Tooth disease, type I

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Aug 21, 2021
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:
RCV000462311.7

Allele description [Variation Report for NM_000530.8(MPZ):c.409G>A (p.Gly137Ser)]

NM_000530.8(MPZ):c.409G>A (p.Gly137Ser)

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.409G>A (p.Gly137Ser)
HGVS:
  • NC_000001.11:g.161306747C>T
  • NG_008055.1:g.8226G>A
  • NM_000530.8:c.409G>AMANE SELECT
  • NM_001315491.2:c.409G>A
  • NP_000521.2:p.Gly137Ser
  • NP_001302420.1:p.Gly137Ser
  • LRG_256t1:c.409G>A
  • LRG_256:g.8226G>A
  • LRG_256p1:p.Gly137Ser
  • NC_000001.10:g.161276537C>T
  • NM_000530.6:c.409G>A
  • P25189:p.Gly137Ser
Protein change:
G137S; GLY137SER
Links:
UniProtKB: P25189#VAR_004540; OMIM: 159440.0008; dbSNP: rs121913588
NCBI 1000 Genomes Browser:
rs121913588
Molecular consequence:
  • NM_000530.8:c.409G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001315491.2:c.409G>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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000552939Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Aug 21, 2021) 		germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Myelin protein zero (MPZ) gene mutations in nonduplication type 1 Charcot-Marie-Tooth disease.

Roa BB, Warner LE, Garcia CA, Russo D, Lovelace R, Chance PF, Lupski JR.

Hum Mutat. 1996;7(1):36-45.

PubMed [citation]
PMID:
8664899

Screening for mutations in a genetically heterogeneous disorder: DHPLC versus DNA sequence for mutation detection in multiple genes causing Charcot-Marie-Tooth neuropathy.

Takashima H, Boerkoel CF, Lupski JR.

Genet Med. 2001 Sep-Oct;3(5):335-42.

PubMed [citation]
PMID:
11545686
See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000552939.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

This sequence change replaces glycine with serine at codon 137 of the MPZ protein (p.Gly137Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 8664899, 11545686, 26310628, Invitae). ClinVar contains an entry for this variant (Variation ID: 14173). Experimental studies have shown that this variant does not substantially affect MPZ protein function (PMID: 29687021). This variant disrupts the p.Gly137 amino acid residue in MPZ. Other variant(s) that disrupt this residue have been observed in individuals with MPZ-related conditions (PMID: 21326314, 24053775), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024