U.S. flag

An official website of the United States government

NM_170707.4(LMNA):c.1357C>T (p.Arg453Trp) AND Dilated cardiomyopathy 1A

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Feb 19, 2020
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:
RCV001095717.6

Allele description [Variation Report for NM_170707.4(LMNA):c.1357C>T (p.Arg453Trp)]

NM_170707.4(LMNA):c.1357C>T (p.Arg453Trp)

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.1357C>T (p.Arg453Trp)
HGVS:
  • NC_000001.11:g.156136413C>T
  • NG_008692.2:g.58841C>T
  • NM_001257374.3:c.1021C>T
  • NM_001282624.2:c.1114C>T
  • NM_001282625.2:c.1357C>T
  • NM_001282626.2:c.1357C>T
  • NM_005572.4:c.1357C>T
  • NM_170707.4:c.1357C>TMANE SELECT
  • NM_170708.4:c.1357C>T
  • NP_001244303.1:p.Arg341Trp
  • NP_001269553.1:p.Arg372Trp
  • NP_001269554.1:p.Arg453Trp
  • NP_001269555.1:p.Arg453Trp
  • NP_005563.1:p.Arg453Trp
  • NP_733821.1:p.Arg453Trp
  • NP_733822.1:p.Arg453Trp
  • LRG_254t2:c.1357C>T
  • LRG_254:g.58841C>T
  • NC_000001.10:g.156106204C>T
  • NM_005572.4:c.1357C>T
  • NM_170707.2:c.1357C>T
  • NM_170707.3:c.1357C>T
  • P02545:p.Arg453Trp
Protein change:
R341W; ARG453TRP
Links:
UniProtKB: P02545#VAR_009988; OMIM: 150330.0002; dbSNP: rs58932704
NCBI 1000 Genomes Browser:
rs58932704
Molecular consequence:
  • NM_001257374.3:c.1021C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001282624.2:c.1114C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001282625.2:c.1357C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001282626.2:c.1357C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_005572.4:c.1357C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_170707.4:c.1357C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_170708.4:c.1357C>T - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
functionally_abnormal [Sequence Ontology: SO:0002218]

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001251555Illumina Laboratory Services, Illumina
criteria provided, single submitter

(ICSLVariantClassificationCriteria RUGD 01 April 2020)		Likely pathogenic
(Feb 19, 2020) 		unknownclinical testing

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

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Early-Onset LMNA-Associated Muscular Dystrophy with Later Involvement of Contracture.

Lee Y, Lee JH, Park HJ, Choi YC.

J Clin Neurol. 2017 Oct;13(4):405-410. doi: 10.3988/jcn.2017.13.4.405.

PubMed [citation]
PMID:
29057633
PMCID:
PMC5653629

A comprehensive genetic diagnosis of Chinese muscular dystrophy and congenital myopathy patients by targeted next-generation sequencing.

Dai Y, Wei X, Zhao Y, Ren H, Lan Z, Yang Y, Chen L, Cui L.

Neuromuscul Disord. 2015 Aug;25(8):617-24. doi: 10.1016/j.nmd.2015.03.002. Epub 2015 Mar 17.

PubMed [citation]
PMID:
25987458
See all PubMed Citations (5)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV001251555.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

The LMNA c.1357C>T (p.Arg453Trp) variant is a missense variant. A literature search was performed for the gene, cDNA change, and amino acid change. No publications reporting this variant in association with isolated dilated cardiomyopathy were found based on this search. However, multiple publications report the variant in association with various types of muscular dystrophy with cardiac manifestations (Bonne et al. 1999; Astejada et al. 2007; Dai et al. 2015; Lee et al. 2017). The variant is not found in the Genome Aggregation Database in a region of good sequencing coverage, which suggests the variant is rare. Functional studies in mouse myoblast C2C12 cells expressing the p.Arg453Trp variant showed poor cell differentiation, improper cell cycle exit, and excessive committment to apoptosis (Favreau et al. 2004). The Arg453 residue lies within the laminin tail domain, a region that may be involved in protein or DNA binding, and in silico analyses suggest the variant is deleterious. Based on the evidence and the application of the ACMG criteria, the p.Arg453Trp variant is classified as likely pathogenic for dilated cardiomyopathy.

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

Last Updated: Nov 24, 2024