NM_000304.4(PMP22):c.351C>A (p.Tyr117Ter) AND Charcot-Marie-Tooth disease, type I

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 14, 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:: RCV001050022.5

Allele description [Variation Report for NM_000304.4(PMP22):c.351C>A (p.Tyr117Ter)]

NM_000304.4(PMP22):c.351C>A (p.Tyr117Ter)

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.351C>A (p.Tyr117Ter)

HGVS:

NC_000017.11:g.15231049G>T
NG_007949.1:g.39279C>A
NM_000304.4:c.351C>AMANE SELECT
NM_001281455.2:c.351C>A
NM_001281456.2:c.351C>A
NM_153321.3:c.351C>A
NM_153322.3:c.351C>A
NP_000295.1:p.Tyr117Ter
NP_001268384.1:p.Tyr117Ter
NP_001268385.1:p.Tyr117Ter
NP_696996.1:p.Tyr117Ter
NP_696997.1:p.Tyr117Ter
LRG_263:g.39279C>A
NC_000017.10:g.15134366G>T
NM_000304.3:c.351C>A
NR_104017.2:n.446C>A
NR_104018.2:n.346C>A

Protein change:

Y117*

Links:

dbSNP: rs1906290133

NCBI 1000 Genomes Browser:

rs1906290133

Molecular consequence:

NR_104017.2:n.446C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104018.2:n.346C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000304.4:c.351C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001281455.2:c.351C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001281456.2:c.351C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_153321.3:c.351C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_153322.3:c.351C>A - nonsense - [Sequence Ontology: SO:0001587]

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001214108	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 14, 2019)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23965407, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001214108

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 14, 2019)

germline

clinical testing

PubMed (2)
[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

Hereditary neuropathy with liability to pressure palsy: two cases of difficult diagnosis.

Beydoun SR, Cho J.

J Clin Neuromuscul Dis. 2013 Sep;15(1):28-33. doi: 10.1097/CND.0b013e31829e22fe.

PubMed [citation]

PMID:: 23965407

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001214108.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the PMP22 protein. Other variant(s) that disrupt this region (p.Leu145Argfs*10) have been determined to be pathogenic (PMID: 23965407,¬†21252112,¬†21149811). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant has not been reported in the literature in individuals with PMP22-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the PMP22 gene (p.Tyr117*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 44 amino acids of the PMP22 protein.

#	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

ClinVar

Relating variation to medicine