NM_170707.4(LMNA):c.1279C>T (p.Arg427Cys) AND Primary dilated cardiomyopathy

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 5, 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:: RCV003996715.1

Allele description

NM_170707.4(LMNA):c.1279C>T (p.Arg427Cys)

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.1279C>T (p.Arg427Cys)

Other names:

p.R427C:CGC>TGC

HGVS:

NC_000001.11:g.156136335C>T
NG_008692.2:g.58763C>T
NM_001257374.3:c.943C>T
NM_001282624.2:c.1036C>T
NM_001282625.2:c.1279C>T
NM_001282626.2:c.1279C>T
NM_005572.4:c.1279C>T
NM_170707.4:c.1279C>TMANE SELECT
NM_170708.4:c.1279C>T
NP_001244303.1:p.Arg315Cys
NP_001269553.1:p.Arg346Cys
NP_001269554.1:p.Arg427Cys
NP_001269555.1:p.Arg427Cys
NP_005563.1:p.Arg427Cys
NP_733821.1:p.Arg427Cys
NP_733822.1:p.Arg427Cys
LRG_254t2:c.1279C>T
LRG_254:g.58763C>T
NC_000001.10:g.156106126C>T
NM_170707.2:c.1279C>T
NM_170707.3:c.1279C>T

Protein change:

R315C

Links:

dbSNP: rs373584456

NCBI 1000 Genomes Browser:

rs373584456

Molecular consequence:

NM_001257374.3:c.943C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001282624.2:c.1036C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001282625.2:c.1279C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001282626.2:c.1279C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_005572.4:c.1279C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_170707.4:c.1279C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_170708.4:c.1279C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004814357	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Sep 5, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004814357

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Sep 5, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	13	not provided	not provided	108544	not provided	clinical 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 All of Us Research Program, National Institutes of Health, SCV004814357.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	13	not provided	not provided	clinical testing	PubMed (1)

Description

This missense variant replaces arginine with cysteine at codon 427 of the LMNA protein. 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). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 7/282184 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	108544	not provided	not provided		13	not provided	not provided	not provided

Last Updated: May 1, 2024

ClinVar

Relating variation to medicine