NM_170707.4(LMNA):c.481G>A (p.Glu161Lys) AND Cardiovascular phenotype

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 19, 2023
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:: RCV004018635.1

Allele description [Variation Report for NM_170707.4(LMNA):c.481G>A (p.Glu161Lys)]

NM_170707.4(LMNA):c.481G>A (p.Glu161Lys)

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.481G>A (p.Glu161Lys)

Other names:

p.E161K:GAG>AAG

HGVS:

NC_000001.11:g.156130741G>A
NG_008692.2:g.53169G>A
NM_001257374.3:c.145G>A
NM_001282624.2:c.238G>A
NM_001282625.2:c.481G>A
NM_001282626.2:c.481G>A
NM_005572.4:c.481G>A
NM_170707.4:c.481G>AMANE SELECT
NM_170708.4:c.481G>A
NP_001244303.1:p.Glu49Lys
NP_001269553.1:p.Glu80Lys
NP_001269554.1:p.Glu161Lys
NP_001269555.1:p.Glu161Lys
NP_005563.1:p.Glu161Lys
NP_733821.1:p.Glu161Lys
NP_733822.1:p.Glu161Lys
LRG_254t2:c.481G>A
LRG_254:g.53169G>A
NC_000001.10:g.156100532G>A
NM_170707.2:c.481G>A
NM_170707.3:c.481G>A
P02545:p.Glu161Lys
c.481G>A

Protein change:

E161K; GLU161LYS

Links:

UniProtKB: P02545#VAR_017660; OMIM: 150330.0028; dbSNP: rs28933093

NCBI 1000 Genomes Browser:

rs28933093

Molecular consequence:

NM_001257374.3:c.145G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282624.2:c.238G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282625.2:c.481G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282626.2:c.481G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_005572.4:c.481G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_170707.4:c.481G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_170708.4:c.481G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005030794	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Dec 19, 2023)	germline	clinical testing	PubMed (13) [See all records that cite these PMIDs] 12920062, 17334235, 18795223, 18926329, 23701190, 24386194, 27532257, 29432544, 31402444, 31514951, 32021920, 32880476, 34768595 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005030794

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Dec 19, 2023)

germline

clinical testing

PubMed (13)
[See all records that cite these PMIDs]

Citation Link

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

Expanding the phenotype of LMNA mutations in dilated cardiomyopathy and functional consequences of these mutations.

Sébillon P, Bouchier C, Bidot LD, Bonne G, Ahamed K, Charron P, Drouin-Garraud V, Millaire A, Desrumeaux G, Benaïche A, Charniot JC, Schwartz K, Villard E, Komajda M.

J Med Genet. 2003 Aug;40(8):560-7.

PubMed [citation]

PMID:: 12920062
PMCID:: PMC1735561

Lamin A/C mutations associated with familial and sporadic cases of dilated cardiomyopathy in Koreans.

Song K, Dubé MP, Lim J, Hwang I, Lee I, Kim JJ.

Exp Mol Med. 2007 Feb 28;39(1):114-20.

PubMed [citation]

PMID:: 17334235

See all PubMed Citations (13)

Details of each submission

From Ambry Genetics, SCV005030794.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (13)

Description

The p.E161K pathogenic mutation (also known as c.481G>A), located in coding exon 2 of the LMNA gene, results from a G to A substitution at nucleotide position 481. The glutamic acid at codon 161 is replaced by lysine, an amino acid with similar properties. This alteration has been reported in probands with a history of LMNA-related disease (Pasotti M et al. J Am Coll Cardiol, 2008 Oct;52:1250-60; Perrot A et al. Basic Res Cardiol, 2009 Jan;104:90-9; Walsh R et al. Genet Med, 2017 Feb;19:192-203; Gigli M et al. J Am Coll Cardiol, 2019 Sep;74:1480-1490; Ferradini V et al. J Clin Med, 2021 Oct;10:; Ambry internal data). In addition, studies show this variant has an impact on protein function (Bhattacharjee P et al. Biochemistry, 2013 Jun;52:4229-41; Laurini E et al. Cardiovasc Res, 2018 May;114:846-857). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

#	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: Dec 22, 2024

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