NM_170707.4(LMNA):c.695G>A (p.Gly232Glu) AND Charcot-Marie-Tooth disease type 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 25, 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:: RCV001052813.8

Allele description [Variation Report for NM_170707.4(LMNA):c.695G>A (p.Gly232Glu)]

NM_170707.4(LMNA):c.695G>A (p.Gly232Glu)

Gene:

LMNA:lamin A/C [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q22

Genomic location:

Preferred name:

NM_170707.4(LMNA):c.695G>A (p.Gly232Glu)

HGVS:

NC_000001.11:g.156134860G>A
NG_008692.2:g.57288G>A
NM_001257374.3:c.359G>A
NM_001282624.2:c.452G>A
NM_001282625.2:c.695G>A
NM_001282626.2:c.695G>A
NM_005572.4:c.695G>A
NM_170707.4:c.695G>AMANE SELECT
NM_170708.4:c.695G>A
NP_001244303.1:p.Gly120Glu
NP_001269553.1:p.Gly151Glu
NP_001269554.1:p.Gly232Glu
NP_001269555.1:p.Gly232Glu
NP_005563.1:p.Gly232Glu
NP_733821.1:p.Gly232Glu
NP_733822.1:p.Gly232Glu
LRG_254t2:c.695G>A
LRG_254:g.57288G>A
NC_000001.10:g.156104651G>A
NM_170707.2:c.695G>A
NM_170707.3:c.695G>A
P02545:p.Gly232Glu

Protein change:

G120E

Links:

UniProtKB: P02545#VAR_039771; dbSNP: rs57207746

NCBI 1000 Genomes Browser:

rs57207746

Molecular consequence:

NM_001257374.3:c.359G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282624.2:c.452G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282625.2:c.695G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282626.2:c.695G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_005572.4:c.695G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_170707.4:c.695G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_170708.4:c.695G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Charcot-Marie-Tooth disease type 2
Synonyms:: Charcot-Marie-Tooth, Type 2
Identifiers:: MONDO: MONDO:0018993; MedGen: C0270914

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001217041	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 25, 2019)	germline	clinical testing	PubMed (10) [See all records that cite these PMIDs] 18564364, 24349489, 25982065, 23077635, 16772334, 29676528, 29753763, 29893365, 10939567, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001217041

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 25, 2019)

germline

clinical testing

PubMed (10)
[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

Laminopathies in Russian families.

Rudenskaya GE, Polyakov AV, Tverskaya SM, Zaklyazminskaya EV, Chukhrova AL, Groznova OE, Ginter EK.

Clin Genet. 2008 Aug;74(2):127-33. doi: 10.1111/j.1399-0004.2008.01045.x. Epub 2008 Jun 28.

PubMed [citation]

PMID:: 18564364

Whole-exome sequencing to identify a novel LMNA gene mutation associated with inherited cardiac conduction disease.

Lai CC, Yeh YH, Hsieh WP, Kuo CT, Wang WC, Chu CH, Hung CL, Cheng CY, Tsai HY, Lee JL, Tang CY, Hsu LA.

PLoS One. 2013;8(12):e83322. doi: 10.1371/journal.pone.0083322.

PubMed [citation]

PMID:: 24349489
PMCID:: PMC3861486

See all PubMed Citations (10)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001217041.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (10)

Description

This sequence change replaces glycine with glutamic acid at codon 232 of the LMNA protein (p.Gly232Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly232 amino acid residue in LMNA. Other variant(s) that disrupt this residue have been observed in individuals with LMNA-related conditions (PMID: 18564364, 24349489), which suggests that this may be a clinically significant amino acid residue. This variant has been reported to affect LMNA protein function (PMID: 25982065, 23077635, 16772334, 29676528, 29753763). This variant has been observed in individual(s) with childhood-onset muscular dystrophy (PMID: 29893365, 10939567). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 66925). This variant is not present in population databases (ExAC no frequency).

#	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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