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

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jun 5, 2019
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:: RCV001221866.4

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001393934	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jun 5, 2019)	germline	clinical testing	PubMed (13) [See all records that cite these PMIDs] 9544841, 12901701, 8995589, 26102530, 18795802, 25385046, 10078969, 15474367, 9425015, 15537650, 10982389, 26392352, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001393934

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jun 5, 2019)

germline

clinical testing

PubMed (13)
[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 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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001393934.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical 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.

#	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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