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NM_170707.4(LMNA):c.1027C>T (p.Arg343Trp) AND Primary dilated cardiomyopathy

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 18, 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:
RCV004001748.2

Allele description [Variation Report for NM_170707.4(LMNA):c.1027C>T (p.Arg343Trp)]

NM_170707.4(LMNA):c.1027C>T (p.Arg343Trp)

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.1027C>T (p.Arg343Trp)
HGVS:
  • NC_000001.11:g.156135991C>T
  • NG_008692.2:g.58419C>T
  • NM_001257374.3:c.691C>T
  • NM_001282624.2:c.784C>T
  • NM_001282625.2:c.1027C>T
  • NM_001282626.2:c.1027C>T
  • NM_005572.4:c.1027C>T
  • NM_170707.4:c.1027C>TMANE SELECT
  • NM_170708.4:c.1027C>T
  • NP_001244303.1:p.Arg231Trp
  • NP_001269553.1:p.Arg262Trp
  • NP_001269554.1:p.Arg343Trp
  • NP_001269555.1:p.Arg343Trp
  • NP_005563.1:p.Arg343Trp
  • NP_005563.1:p.Arg343Trp
  • NP_733821.1:p.Arg343Trp
  • NP_733822.1:p.Arg343Trp
  • LRG_254t1:c.1027C>T
  • LRG_254t2:c.1027C>T
  • LRG_254:g.58419C>T
  • LRG_254p1:p.Arg343Trp
  • NC_000001.10:g.156105782C>T
  • NM_005572.3:c.1027C>T
  • NM_170707.2:c.1027C>T
  • NM_170707.3:c.1027C>T
Protein change:
R231W
Links:
dbSNP: rs749784223
NCBI 1000 Genomes Browser:
rs749784223
Molecular consequence:
  • NM_001257374.3:c.691C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001282624.2:c.784C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001282625.2:c.1027C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001282626.2:c.1027C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_005572.4:c.1027C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_170707.4:c.1027C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_170708.4:c.1027C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
8

Condition(s)

Name:
Primary dilated cardiomyopathy (DCM)
Synonyms:
Dilated Cardiomyopathy
Identifiers:
EFO: EFO_0000407; MONDO: MONDO:0005021; MeSH: D002311; MedGen: C0007193; Human Phenotype Ontology: HP:0001644

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004817771All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain Significance
(Dec 18, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown8not providednot provided108544not providedclinical testing

Citations

PubMed

[A case report of thoracic foreign body resembling fungus ball on chest X-P].

Sasai T, Sakakibara S, Kaji M, Yamada Y, Nitta T, Yamate N, Tanaka S, Shouji T.

Kyobu Geka. 1989 Feb;42(2):138-40. Japanese.

PubMed [citation]
PMID:
2733290

Comprehensive genetic sequence and copy number analysis for Charcot-Marie-Tooth disease in a Canadian cohort of 2517 patients.

Volodarsky M, Kerkhof J, Stuart A, Levy M, Brady LI, Tarnopolsky M, Lin H, Ainsworth P, Sadikovic B.

J Med Genet. 2021 Apr;58(4):284-288. doi: 10.1136/jmedgenet-2019-106641. Epub 2020 May 6.

PubMed [citation]
PMID:
32376792
See all PubMed Citations (3)

Details of each submission

From All of Us Research Program, National Institutes of Health, SCV004817771.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided8not providednot providedclinical testing PubMed (3)

Description

This missense variant replaces arginine with tryptophan at codon 343 of the lamin A/C proteins. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with Charcot-Marie-Tooth disease (PMID: 32376792) and in an individual affected with sudden cardiac death (PMID: 2733290). This variant has been identified in 1/251046 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown108544not providednot provided8not providednot providednot provided

Last Updated: May 7, 2024