NM_000304.4(PMP22):c.434del (p.Leu145fs) AND Charcot-Marie-Tooth disease, type I

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 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:: RCV000638170.8

Allele description [Variation Report for NM_000304.4(PMP22):c.434del (p.Leu145fs)]

NM_000304.4(PMP22):c.434del (p.Leu145fs)

Gene:

PMP22:peripheral myelin protein 22 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

17p12

Genomic location:

Preferred name:

NM_000304.4(PMP22):c.434del (p.Leu145fs)

HGVS:

NC_000017.11:g.15230966del
NG_007949.1:g.39362del
NM_000304.4:c.434delMANE SELECT
NM_001281455.2:c.434del
NM_001281456.2:c.434del
NM_153321.3:c.434del
NM_153322.3:c.434del
NP_000295.1:p.Leu145fs
NP_001268384.1:p.Leu145fs
NP_001268385.1:p.Leu145fs
NP_696996.1:p.Leu145fs
NP_696997.1:p.Leu145fs
LRG_263t1:c.434del
LRG_263:g.39362del
NC_000017.10:g.15134283del
NM_000304.2:c.434delT
NM_000304.3:c.434del
NM_000304.3:c.434delT
NM_000304.4:c.434delTMANE SELECT
NR_104017.2:n.529del
NR_104018.2:n.429del

Protein change:

L145fs

Links:

dbSNP: rs863225029

NCBI 1000 Genomes Browser:

rs863225029

Molecular consequence:

NM_000304.4:c.434del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281455.2:c.434del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281456.2:c.434del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_153321.3:c.434del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_153322.3:c.434del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_104017.2:n.529del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104018.2:n.429del - 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
SCV000759656	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 13, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 21149811, 21252112, 23965407, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000759656

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 13, 2023)

germline

clinical testing

PubMed (4)
[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

Analyzing histopathological features of rare charcot-marie-tooth neuropathies to unravel their pathogenesis.

Benedetti S, Previtali SC, Coviello S, Scarlato M, Cerri F, Di Pierri E, Piantoni L, Spiga I, Fazio R, Riva N, Natali Sora MG, Dacci P, Malaguti MC, Munerati E, Grimaldi LM, Marrosu MG, De Pellegrin M, Ferrari M, Comi G, Quattrini A, Bolino A.

Arch Neurol. 2010 Dec;67(12):1498-505. doi: 10.1001/archneurol.2010.303.

PubMed [citation]

PMID:: 21149811

Inherited demyelinating neuropathies with micromutations of peripheral myelin protein 22 gene.

Taioli F, Cabrini I, Cavallaro T, Acler M, Fabrizi GM.

Brain. 2011 Feb;134(Pt 2):608-17. doi: 10.1093/brain/awq374. Epub 2011 Jan 19.

PubMed [citation]

PMID:: 21252112

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000759656.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Leu145Argfs*10) in the PMP22 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 16 amino acid(s) of the PMP22 protein. This variant is present in population databases (no rsID available, gnomAD 0.003%). This premature translational stop signal has been observed in individuals with hereditary neuropathy with liability to pressure palsy (HNPP) (PMID: 21149811, 21252112, 23965407). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 217238). For these reasons, this variant has been classified as 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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