NM_000399.5(EGR2):c.1225C>T (p.Arg409Trp) AND Charcot-Marie-Tooth disease type 1D

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Jan 6, 2016
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000018234.29

Allele description [Variation Report for NM_000399.5(EGR2):c.1225C>T (p.Arg409Trp)]

NM_000399.5(EGR2):c.1225C>T (p.Arg409Trp)

Gene:

EGR2:early growth response 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q21.3

Genomic location:

Preferred name:

NM_000399.5(EGR2):c.1225C>T (p.Arg409Trp)

HGVS:

NC_000010.11:g.62813413G>A
NG_008936.2:g.111488C>T
NM_000399.4:c.1225C>T
NM_000399.5:c.1225C>TMANE SELECT
NM_001136177.3:c.1225C>T
NM_001136178.2:c.1225C>T
NM_001136179.3:c.1075C>T
NM_001321037.2:c.1075C>T
NP_000390.2:p.Arg409Trp
NP_001129649.1:p.Arg409Trp
NP_001129650.1:p.Arg409Trp
NP_001129651.1:p.Arg359Trp
NP_001307966.1:p.Arg359Trp
LRG_239t1:c.1225C>T
LRG_239:g.111488C>T
NC_000010.10:g.64573173G>A
NM_000399.3:c.1225C>T
P11161:p.Arg409Trp

Protein change:

R359W; ARG409TRP

Links:

UniProtKB: P11161#VAR_007738; OMIM: 129010.0002; dbSNP: rs104894159

NCBI 1000 Genomes Browser:

rs104894159

Molecular consequence:

NM_000399.5:c.1225C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001136177.3:c.1225C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001136178.2:c.1225C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001136179.3:c.1075C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001321037.2:c.1075C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Charcot-Marie-Tooth disease type 1D
Synonyms:: CHARCOT-MARIE-TOOTH NEUROPATHY, TYPE 1D; HMSN ID; CMT 1D; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011890; MedGen: C1843247; Orphanet: 101084; OMIM: 607678

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000038513	OMIM	no assertion criteria provided	Pathogenic (Jan 14, 2003)	germline	literature only	PubMed (1) [See all records that cite this PMID] Warner, L. E., Mancias, P., Butler, I., Lupski, J. R. Mutation in the early growth response 2 (EGR2) transcription factor associated with recessive congenital hypomyelinating neuropathy (CHN). (Abstract) Am. J. Hum. Genet. 61 (suppl.): A350-only, 1997.,
SCV000055672	GeneReviews	no classification provided	not provided	unknown	literature only	PubMed (1) [See all records that cite this PMID]
SCV004174375	Inherited Neuropathy Consortium Ii, University Of Miami	no assertion criteria provided	Uncertain significance (Jan 6, 2016)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000038513

OMIM

no assertion criteria provided

Pathogenic
(Jan 14, 2003)

germline

literature only

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

Warner, L. E., Mancias, P., Butler, I., Lupski, J. R. Mutation in the early growth response 2 (EGR2) transcription factor associated with recessive congenital hypomyelinating neuropathy (CHN). (Abstract) Am. J. Hum. Genet. 61 (suppl.): A350-only, 1997.,

SCV000055672

GeneReviews

no classification provided

not provided

unknown

literature only

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

SCV004174375

Inherited Neuropathy Consortium Ii, University Of Miami

no assertion criteria provided

Uncertain significance
(Jan 6, 2016)

germline

literature only

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	literature only
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Mutation of a putative protein degradation gene LITAF/SIMPLE in Charcot-Marie-Tooth disease 1C.

Street VA, Bennett CL, Goldy JD, Shirk AJ, Kleopa KA, Tempel BL, Lipe HP, Scherer SS, Bird TD, Chance PF.

Neurology. 2003 Jan 14;60(1):22-6.

PubMed [citation]

PMID:: 12525712

Charcot-Marie-Tooth Neuropathy Type 1 – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY.

Bird TD.

1998 Aug 31 [updated 2015 Mar 26]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(®) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024.

PubMed [citation]

PMID:: 20301384

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000038513.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a family (HOU184) in which the proband, his mother, and his half sister had demyelinating Charcot-Marie-Tooth disease type 1D (CMT1D; 607678), Warner et al. (1998) found that affected members had a heterozygous C-to-T transition in the EGR2 gene that predicted an arg409-to-trp (R409W) substitution within the third zinc finger of the protein. CMT1 was diagnosed in the proband at age 15 years. His mother had been diagnosed at the age of 37 years, but described her initial symptoms as occurring during her first pregnancy at age 18 years. Nerve conduction velocities were markedly slowed.

The form of Charcot-Marie-Tooth disease type 1 caused by mutations in the EGR2 gene was referred to by Street et al. (2003) as CMT1D.

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

From GeneReviews, SCV000055672.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

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

From Inherited Neuropathy Consortium Ii, University Of Miami, SCV004174375.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

#	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: Sep 29, 2024

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