NM_170707.4(LMNA):c.565C>T (p.Arg189Trp) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 23, 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:: RCV002345365.4

Allele description [Variation Report for NM_170707.4(LMNA):c.565C>T (p.Arg189Trp)]

NM_170707.4(LMNA):c.565C>T (p.Arg189Trp)

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.565C>T (p.Arg189Trp)

HGVS:

NC_000001.11:g.156134454C>T
NG_008692.2:g.56882C>T
NM_001257374.3:c.229C>T
NM_001282624.2:c.322C>T
NM_001282625.2:c.565C>T
NM_001282626.2:c.565C>T
NM_005572.4:c.565C>T
NM_170707.4:c.565C>TMANE SELECT
NM_170708.4:c.565C>T
NP_001244303.1:p.Arg77Trp
NP_001269553.1:p.Arg108Trp
NP_001269554.1:p.Arg189Trp
NP_001269555.1:p.Arg189Trp
NP_005563.1:p.Arg189Trp
NP_733821.1:p.Arg189Trp
NP_733822.1:p.Arg189Trp
LRG_254t2:c.565C>T
LRG_254:g.56882C>T
NC_000001.10:g.156104245C>T
NM_001257374.1:c.229C>T
NM_170707.2:c.565C>T
NM_170707.3:c.565C>T

Protein change:

R108W

Links:

dbSNP: rs267607626

NCBI 1000 Genomes Browser:

rs267607626

Molecular consequence:

NM_001257374.3:c.229C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001282624.2:c.322C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001282625.2:c.565C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001282626.2:c.565C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_005572.4:c.565C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_170707.4:c.565C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_170708.4:c.565C>T - 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
SCV002653792	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Mar 23, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 20307303, 22326558, 23299917, 23328570, 34768595 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002653792

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Mar 23, 2023)

germline

clinical testing

PubMed (5)
[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

A novel LMNA mutation (R189W) in familial dilated cardiomyopathy: evidence for a 'hot spot' region at exon 3: a case report.

Botto N, Vittorini S, Colombo MG, Biagini A, Paradossi U, Aquaro G, Andreassi MG.

Cardiovasc Ultrasound. 2010 Mar 22;8:9. doi: 10.1186/1476-7120-8-9.

PubMed [citation]

PMID:: 20307303
PMCID:: PMC2859370

Protein profiling reveals energy metabolism and cytoskeletal protein alterations in LMNA mutation carriers.

Magagnotti C, Bachi A, Zerbini G, Fattore E, Fermo I, Riba M, Previtali SC, Ferrari M, Andolfo A, Benedetti S.

Biochim Biophys Acta. 2012 Jun;1822(6):970-9. doi: 10.1016/j.bbadis.2012.01.014. Epub 2012 Feb 3.

PubMed [citation]

PMID:: 22326558

See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV002653792.3

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

Description

The p.R189W variant (also known as c.565C>T), located in coding exon 3 of the LMNA gene, results from a C to T substitution at nucleotide position 565. The arginine at codon 189 is replaced by tryptophan, an amino acid with dissimilar properties. This variant was detected in an individual with limb-girdle muscular dystrophy, peripheral neuropathy, and dilated cardiomyopathy (DCM), as well as in a female with DCM and family history of sudden cardiac death including two affected obligate carriers (Botto N et al. Cardiovasc Ultrasound, 2010 Mar;8:9; Magagnotti C et al. Biochim. Biophys. Acta, 2012 Jun;1822:970-9). This variant has also been reported in DCM and exome cohorts, but limited or no clinical information was provided (Fontana M et al. JACC Cardiovasc Imaging, 2013 Jan;6:124-6; Andreasen C et al. Eur. J. Hum. Genet., 2013 Sep;21:918-28; Ferradini V et al. J Clin Med, 2021 Oct;10). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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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