NM_000304.4(PMP22):c.341C>T (p.Ala114Val) AND Charcot-Marie-Tooth disease, type IA

Germline classification:: Uncertain significance (2 submissions)
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:: RCV001542602.4

Allele description [Variation Report for NM_000304.4(PMP22):c.341C>T (p.Ala114Val)]

NM_000304.4(PMP22):c.341C>T (p.Ala114Val)

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.341C>T (p.Ala114Val)

HGVS:

NC_000017.11:g.15231059G>A
NG_007949.1:g.39269C>T
NM_000304.4:c.341C>TMANE SELECT
NM_001281455.2:c.341C>T
NM_001281456.2:c.341C>T
NM_153321.3:c.341C>T
NM_153322.3:c.341C>T
NP_000295.1:p.Ala114Val
NP_001268384.1:p.Ala114Val
NP_001268385.1:p.Ala114Val
NP_696996.1:p.Ala114Val
NP_696997.1:p.Ala114Val
LRG_263:g.39269C>T
NC_000017.10:g.15134376G>A
NR_104017.2:n.436C>T
NR_104018.2:n.336C>T

Protein change:

A114V

Links:

dbSNP: rs1217342392

NCBI 1000 Genomes Browser:

rs1217342392

Molecular consequence:

NM_000304.4:c.341C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001281455.2:c.341C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001281456.2:c.341C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_153321.3:c.341C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_153322.3:c.341C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_104017.2:n.436C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104018.2:n.336C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Charcot-Marie-Tooth disease, type IA (CMT1A)
Synonyms:: CHARCOT-MARIE-TOOTH DISEASE, AUTOSOMAL DOMINANT, WITH FOCALLY FOLDED MYELIN SHEATHS, TYPE 1A; CHARCOT-MARIE-TOOTH NEUROPATHY, TYPE 1A; HEREDITARY MOTOR AND SENSORY NEUROPATHY IA; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007309; MedGen: C0270911; Orphanet: 101081; OMIM: 118220

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001760395	Genomics England Pilot Project, Genomics England	no assertion criteria provided (ACGS Guidelines, 2016)	Likely pathogenic	germline	clinical testing	Citation Link,
SCV004047573	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance	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

SCV001760395

Genomics England Pilot Project, Genomics England

no assertion criteria provided

(ACGS Guidelines, 2016)

Likely pathogenic

germline

clinical testing

Citation Link,

SCV004047573

Neuberg Centre For Genomic Medicine, NCGM

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Genomics England Pilot Project, Genomics England, SCV001760395.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Neuberg Centre For Genomic Medicine, NCGM, SCV004047573.1

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

Description

The missense variant c.341C>T (p.Ala114Val) in PMP22 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant has been reported to the ClinVar database as Likely Pathogenic. The p.Ala114Val variant is novel (not in any individuals) in 1000 Genomes and allele frequency of 0.0003989% is reported in gnomAD. The amino acid Ala at position 114 is changed to a Val changing protein sequence and it might alter its composition and physico-chemical properties. The amino acid change p.Ala114Val in PMP22 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 6, 2024

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