NM_170707.4(LMNA):c.1567G>A (p.Gly523Arg) AND Charcot-Marie-Tooth disease type 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 1, 2022
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:: RCV000474372.8

Allele description [Variation Report for NM_170707.4(LMNA):c.1567G>A (p.Gly523Arg)]

NM_170707.4(LMNA):c.1567G>A (p.Gly523Arg)

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.1567G>A (p.Gly523Arg)

HGVS:

NC_000001.11:g.156137191G>A
NG_008692.2:g.59619G>A
NM_001257374.3:c.1231G>A
NM_001282624.2:c.1324G>A
NM_001282625.2:c.1567G>A
NM_001282626.2:c.1567G>A
NM_005572.4:c.1567G>A
NM_170707.4:c.1567G>AMANE SELECT
NM_170708.4:c.1567G>A
NP_001244303.1:p.Gly411Arg
NP_001269553.1:p.Gly442Arg
NP_001269554.1:p.Gly523Arg
NP_001269555.1:p.Gly523Arg
NP_005563.1:p.Gly523Arg
NP_733821.1:p.Gly523Arg
NP_733822.1:p.Gly523Arg
LRG_254t2:c.1567G>A
LRG_254:g.59619G>A
NC_000001.10:g.156106982G>A
NM_170707.2:c.1567G>A
NM_170707.3:c.1567G>A
P02545:p.Gly523Arg
c.1567G>A

Protein change:

G411R

Links:

UniProtKB: P02545#VAR_067258; dbSNP: rs201583907

NCBI 1000 Genomes Browser:

rs201583907

Molecular consequence:

NM_001257374.3:c.1231G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282624.2:c.1324G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282625.2:c.1567G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282626.2:c.1567G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_005572.4:c.1567G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_170707.4:c.1567G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_170708.4:c.1567G>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

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
SCV000548848	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 1, 2022)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 19318026, 24503780, 26404900, 29970176, 32041611, 24623722, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000548848

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 1, 2022)

germline

clinical testing

PubMed (7)
[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

Validation of high-resolution DNA melting analysis for mutation scanning of the LMNA gene.

Millat G, Chanavat V, Julia S, Crehalet H, Bouvagnet P, Rousson R.

Clin Biochem. 2009 Jun;42(9):892-8. doi: 10.1016/j.clinbiochem.2009.01.016. Epub 2009 Feb 6.

PubMed [citation]

PMID:: 19318026

The landscape of genetic variation in dilated cardiomyopathy as surveyed by clinical DNA sequencing.

Pugh TJ, Kelly MA, Gowrisankar S, Hynes E, Seidman MA, Baxter SM, Bowser M, Harrison B, Aaron D, Mahanta LM, Lakdawala NK, McDermott G, White ET, Rehm HL, Lebo M, Funke BH.

Genet Med. 2014 Aug;16(8):601-8. doi: 10.1038/gim.2013.204. Epub 2014 Feb 6.

PubMed [citation]

PMID:: 24503780

See all PubMed Citations (7)

Details of each submission

From Invitae, SCV000548848.9

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 523 of the LMNA protein (p.Gly523Arg). This variant is present in population databases (rs201583907, gnomAD 0.01%). This missense change has been observed in individual(s) with limb girdle muscular dystrophy, dilated cardiomyopathy, or dyslipidemias (PMID: 19318026, 24503780, 26404900, 29970176, 32041611). ClinVar contains an entry for this variant (Variation ID: 48045). 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 expected to disrupt LMNA protein function. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on LMNA function (PMID: 24623722). 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.

#	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: May 7, 2024

ClinVar

Relating variation to medicine