NM_000304.4(PMP22):c.376C>G (p.Leu126Val) AND Charcot-Marie-Tooth disease, type I

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 15, 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:: RCV003741925.1

Allele description [Variation Report for NM_000304.4(PMP22):c.376C>G (p.Leu126Val)]

NM_000304.4(PMP22):c.376C>G (p.Leu126Val)

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.376C>G (p.Leu126Val)

HGVS:

NC_000017.11:g.15231024G>C
NG_007949.1:g.39304C>G
NM_000304.4:c.376C>GMANE SELECT
NM_001281455.2:c.376C>G
NM_001281456.2:c.376C>G
NM_153321.3:c.376C>G
NM_153322.3:c.376C>G
NP_000295.1:p.Leu126Val
NP_000295.1:p.Leu126Val
NP_001268384.1:p.Leu126Val
NP_001268385.1:p.Leu126Val
NP_696996.1:p.Leu126Val
NP_696997.1:p.Leu126Val
LRG_263t1:c.376C>G
LRG_263:g.39304C>G
LRG_263p1:p.Leu126Val
NC_000017.10:g.15134341G>C
NM_000304.2:c.376C>G
NR_104017.2:n.471C>G
NR_104018.2:n.371C>G

Protein change:

L126V

Molecular consequence:

NM_000304.4:c.376C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001281455.2:c.376C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001281456.2:c.376C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_153321.3:c.376C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_153322.3:c.376C>G - missense variant - [Sequence Ontology: SO:0001583]
NR_104017.2:n.471C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104018.2:n.371C>G - 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

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
SCV004424522	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 15, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004424522

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 15, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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 Invitae, SCV004424522.1

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

Description

This variant has not been reported in the literature in individuals affected with PMP22-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PMP22 protein function. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 126 of the PMP22 protein (p.Leu126Val).

#	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: Feb 28, 2024

ClinVar

Relating variation to medicine