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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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002653792Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Mar 23, 2023) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024