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NM_170707.4(LMNA):c.1129C>T (p.Arg377Cys) AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 29, 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:
RCV003343619.2

Allele description [Variation Report for NM_170707.4(LMNA):c.1129C>T (p.Arg377Cys)]

NM_170707.4(LMNA):c.1129C>T (p.Arg377Cys)

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.1129C>T (p.Arg377Cys)
HGVS:
  • NC_000001.11:g.156136093C>T
  • NG_008692.2:g.58521C>T
  • NM_001257374.3:c.793C>T
  • NM_001282624.2:c.886C>T
  • NM_001282625.2:c.1129C>T
  • NM_001282626.2:c.1129C>T
  • NM_005572.4:c.1129C>T
  • NM_170707.4:c.1129C>TMANE SELECT
  • NM_170708.4:c.1129C>T
  • NP_001244303.1:p.Arg265Cys
  • NP_001269553.1:p.Arg296Cys
  • NP_001269554.1:p.Arg377Cys
  • NP_001269555.1:p.Arg377Cys
  • NP_005563.1:p.Arg377Cys
  • NP_005563.1:p.Arg377Cys
  • NP_733821.1:p.Arg377Cys
  • NP_733822.1:p.Arg377Cys
  • LRG_254t1:c.1129C>T
  • LRG_254t2:c.1129C>T
  • LRG_254:g.58521C>T
  • LRG_254p1:p.Arg377Cys
  • NC_000001.10:g.156105884C>T
  • NM_005572.3:c.1129C>T
  • NM_170707.2:c.1129C>T
  • NM_170707.3:c.1129C>T
  • c.1129C>T
  • p.(Arg377Cys)
Protein change:
R265C
Links:
dbSNP: rs397517889
NCBI 1000 Genomes Browser:
rs397517889
Molecular consequence:
  • NM_001257374.3:c.793C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001282624.2:c.886C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001282625.2:c.1129C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001282626.2:c.1129C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_005572.4:c.1129C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_170707.4:c.1129C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_170708.4:c.1129C>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
SCV004074605Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Jun 29, 2023) 		germlineclinical testing

PubMed (14)
[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

Primary prevention of sudden death in patients with lamin A/C gene mutations.

Meune C, Van Berlo JH, Anselme F, Bonne G, Pinto YM, Duboc D.

N Engl J Med. 2006 Jan 12;354(2):209-10. No abstract available.

PubMed [citation]
PMID:
16407522

Emerinopathy and laminopathy clinical, pathological and molecular features of muscular dystrophy with nuclear envelopathy in Japan.

Astejada MN, Goto K, Nagano A, Ura S, Noguchi S, Nonaka I, Nishino I, Hayashi YK.

Acta Myol. 2007 Dec;26(3):159-64. Review.

PubMed [citation]
PMID:
18646565
PMCID:
PMC2949309
See all PubMed Citations (14)

Details of each submission

From Ambry Genetics, SCV004074605.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (14)

Description

The p.R377C pathogenic mutation (also known as c.1129C>T), located in coding exon 6 of the LMNA gene, results from a C to T substitution at nucleotide position 1129. The arginine at codon 377 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration has been reported in multiple individuals with laminopathies, including dilated cardiomyopathy (DCM), Emery-Dreifuss muscular dystrophy, and limb girdle muscular dystrophy (Deconinck N et al. Neuromuscul Disord, 2010 Aug;20:517-23; Komaki H et al. Neuromuscul Disord, 2011 Aug;21:563-8; Sylvius N et al. FASEB J, 2011 Nov;25:3966-78; Pugh TJ et al. Genet Med, 2014 Aug;16:601-8; Hasselberg NE et al. Eur Heart J, 2018 Mar;39:853-860; Cotta A et al. J Mol Neurosci, 2019 Dec;69:623-627; Krenn M et al. Eur J Neurol, 2022 Jun;29:1815-1824; Pessente GD et al. Front Cardiovasc Med, 2022 Apr;9:823717). Two other alterations at the same codon, p.R377L (c.1130G>T) and p.R377H (c.1130G>A), have been detected in subjects with DCM, as well as in subjects with varying forms of muscular dystrophy, and have been reported to segregate with disease (Muchir A et al. Hum. Mol. Genet., 2000 May;9:1453-9; Ki CS et al. J. Hum. Genet., 2002;47:225-8; Boriani G et al. Stroke, 2003 Apr;34:901-8; Charniot JC et al. Hum. Mutat., 2003 May;21:473-81; Sébillon P et al. J. Med. Genet., 2003 Aug;40:560-7; Rudnik-Schöneborn S et al. Neurogenetics, 2007 Apr;8:137-42; Verdonschot JAJ et al. Circ Genom Precis Med, 2020 10;13:476-487). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is predicted to be deleterious by BayesDel in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Sep 29, 2024