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NM_170707.4(LMNA):c.1129C>T (p.Arg377Cys) AND Dilated cardiomyopathy 1A

Germline classification:
Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:
Aug 1, 2018
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000592134.3

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]
Observations:
1

Condition(s)

Name:
Dilated cardiomyopathy 1A (CMD1A)
Synonyms:
CARDIOMYOPATHY, CONGESTIVE; CARDIOMYOPATHY, DILATED, WITH CONDUCTION DEFECT 1; Idiopathic dilated cardiomyopathy; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007269; MedGen: C1449563; Orphanet: 300751; OMIM: 115200

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000840004Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(May 25, 2017) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV000897957Center of Genomic medicine, Geneva, University Hospital of Geneva
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Aug 1, 2018) 		maternalclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedmaternalyes1not providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine, SCV000840004.1

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

Description

This c.1129C>T (p.Arg377Cys) variant in the LMNA gene has previously been reported in a 49 year old male with a diagnosis and a family history of DCM [PMID 24503780] and was also detected in a 10 y/o female who died of heart failure, with unsteady gait, diagnosed at the age of 7 with DCM [PMID 21632249]. This variant was also detected in a cohort of patients with muscular dystrophy [PMID 18646565] and a cohort of patients with cardiac disease [PMID 23183350]. Additional variants affecting the same amino acid at position 377 (p.Arg377His and p.Arg377Leu) have been reported in patients with cardiomyopathy and muscular dystrophy. Arginine at position 377 of the LMNA protein is highly conserved in mammals and has not been observed in the ExAC database. While not validated for clinical use, the computer-based algorithms SIFT and Polyphen-2 predict this Arg377Cys change to be deleterious. It is thus interpreted as a likely pathogenic variant.

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

From Center of Genomic medicine, Geneva, University Hospital of Geneva, SCV000897957.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1maternalyesnot providednot providednot provided1not providednot providednot provided

Last Updated: Sep 29, 2024