NM_000304.4(PMP22):c.448G>T (p.Gly150Cys) AND Charcot-Marie-Tooth disease, type I

Clinical significance:Likely pathogenic (Last evaluated: Jun 5, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001221866.2

Allele description [Variation Report for NM_000304.4(PMP22):c.448G>T (p.Gly150Cys)]

NM_000304.4(PMP22):c.448G>T (p.Gly150Cys)

Gene:
PMP22:peripheral myelin protein 22 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17p12
Genomic location:
Preferred name:
NM_000304.4(PMP22):c.448G>T (p.Gly150Cys)
HGVS:
  • NC_000017.11:g.15230952C>A
  • NG_007949.1:g.39376G>T
  • NM_000304.4:c.448G>TMANE SELECT
  • NM_001281455.2:c.448G>T
  • NM_001281456.2:c.448G>T
  • NM_153321.3:c.448G>T
  • NM_153322.3:c.448G>T
  • NP_000295.1:p.Gly150Cys
  • NP_001268384.1:p.Gly150Cys
  • NP_001268385.1:p.Gly150Cys
  • NP_696996.1:p.Gly150Cys
  • NP_696997.1:p.Gly150Cys
  • LRG_263:g.39376G>T
  • NC_000017.10:g.15134269C>A
  • NM_000304.3:c.448G>T
  • NR_104017.2:n.543G>T
  • NR_104018.2:n.443G>T
  • Q01453:p.Gly150Cys
Protein change:
G150C; GLY150CYS
Links:
UniProtKB: Q01453#VAR_006378; OMIM: 601097.0013; dbSNP: rs104894624
NCBI 1000 Genomes Browser:
rs104894624
Molecular consequence:
  • NM_000304.4:c.448G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281455.2:c.448G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281456.2:c.448G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_153321.3:c.448G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_153322.3:c.448G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_104017.2:n.543G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_104018.2:n.443G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001393934Invitaecriteria provided, single submitter
Likely pathogenic
(Jun 5, 2019)
germlineclinical testing

PubMed (13)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Novel mutations of the peripheral myelin protein 22 gene in two pedigrees with Dejerine-Sottas disease.

Ikegami T, Ikeda H, Aoyama M, Matsuki T, Imota T, Fukuuchi Y, Amano T, Toyoshima I, Ishihara Y, Endoh H, Hayasaka K.

Hum Genet. 1998 Mar;102(3):294-8.

PubMed [citation]
PMID:
9544841

Phenotypic differences between peripheral myelin protein-22 (PMP22) and myelin protein zero (P0) mutations associated with Charcot-Marie-Tooth-related diseases.

Shames I, Fraser A, Colby J, Orfali W, Snipes GJ.

J Neuropathol Exp Neurol. 2003 Jul;62(7):751-64.

PubMed [citation]
PMID:
12901701
See all PubMed Citations (13)

Details of each submission

From Invitae, SCV001393934.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (13)

Description

This sequence change replaces glycine with cysteine at codon 150 of the PMP22 protein (p.Gly150Cys). The glycine residue is highly conserved and there is a large physicochemical difference between glycine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with Dejerine-Sottas disease in a family (PMID: 9544841). ClinVar contains an entry for this variant (Variation ID: 8439). This variant has been reported to affect PMP22 protein function (PMID: 12901701). This variant disrupts the p.Gly150 amino acid residue in PMP22. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8995589, 26102530, 18795802, 25385046, 10078969, 15474367, 9425015, 15537650, 10982389, 26392352). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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: Oct 30, 2021

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