NM_170707.4(LMNA):c.497G>C (p.Arg166Pro) AND Charcot-Marie-Tooth disease type 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 31, 2024
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:: RCV000556738.11

Allele description [Variation Report for NM_170707.4(LMNA):c.497G>C (p.Arg166Pro)]

NM_170707.4(LMNA):c.497G>C (p.Arg166Pro)

Genes:

LOC126805877:MED14-independent group 3 enhancer GRCh37_chr1:156099693-156100892 [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.497G>C (p.Arg166Pro)

Other names:

p.R166P:CGG>CCG

HGVS:

NC_000001.11:g.156130757G>C
NG_008692.2:g.53185G>C
NM_001257374.3:c.161G>C
NM_001282624.2:c.254G>C
NM_001282625.2:c.497G>C
NM_001282626.2:c.497G>C
NM_005572.4:c.497G>C
NM_170707.4:c.497G>CMANE SELECT
NM_170708.4:c.497G>C
NP_001244303.1:p.Arg54Pro
NP_001269553.1:p.Arg85Pro
NP_001269553.1:p.Arg85Pro
NP_001269554.1:p.Arg166Pro
NP_001269555.1:p.Arg166Pro
NP_005563.1:p.Arg166Pro
NP_733821.1:p.Arg166Pro
NP_733822.1:p.Arg166Pro
LRG_254t2:c.497G>C
LRG_254:g.53185G>C
NC_000001.10:g.156100548G>C
NM_001282624.1:c.254G>C
NM_170707.2:c.497G>C
NM_170707.3:c.497G>C
P02545:p.Arg166Pro

Protein change:

R166P

Links:

UniProtKB: P02545#VAR_070176; dbSNP: rs267607570

NCBI 1000 Genomes Browser:

rs267607570

Molecular consequence:

NM_001257374.3:c.161G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001282624.2:c.254G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001282625.2:c.497G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001282626.2:c.497G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_005572.4:c.497G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_170707.4:c.497G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_170708.4:c.497G>C - 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
SCV000657815	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 31, 2024)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 18585512, 19638735, 26084686, 20160190, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000657815

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 31, 2024)

germline

clinical testing

PubMed (5)
[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

Lamin A/C mutation analysis in a cohort of 324 unrelated patients with idiopathic or familial dilated cardiomyopathy.

Parks SB, Kushner JD, Nauman D, Burgess D, Ludwigsen S, Peterson A, Li D, Jakobs P, Litt M, Porter CB, Rahko PS, Hershberger RE.

Am Heart J. 2008 Jul;156(1):161-9. doi: 10.1016/j.ahj.2008.01.026. Epub 2008 Mar 12.

PubMed [citation]

PMID:: 18585512
PMCID:: PMC2527054

Lamin A/C gene mutations in familial cardiomyopathy with advanced atrioventricular block and arrhythmia.

Saga A, Karibe A, Otomo J, Iwabuchi K, Takahashi T, Kanno H, Kikuchi J, Keitoku M, Shinozaki T, Shimokawa H.

Tohoku J Exp Med. 2009 Aug;218(4):309-16.

PubMed [citation]

PMID:: 19638735

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000657815.9

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 166 of the LMNA protein (p.Arg166Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with familial cardiomyopathy with advanced atrioventricular block and dilated cardiomyopathy (PMID: 18585512, 19638735, 26084686). ClinVar contains an entry for this variant (Variation ID: 66901). 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 with a positive predictive value of 95%. Experimental studies have shown that this missense change affects LMNA function (PMID: 20160190). For these reasons, this variant has been classified as Pathogenic.

#	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

ClinVar

Relating variation to medicine