NM_170707.4(LMNA):c.511A>G (p.Lys171Glu) AND Primary dilated cardiomyopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 10, 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:: RCV004000288.2

Allele description [Variation Report for NM_170707.4(LMNA):c.511A>G (p.Lys171Glu)]

NM_170707.4(LMNA):c.511A>G (p.Lys171Glu)

Genes:

LOC126805877:MED14-independent group 3 enhancer GRCh37_chr1:156099693-156100892 [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.511A>G (p.Lys171Glu)

HGVS:

NC_000001.11:g.156130771A>G
NG_008692.2:g.53199A>G
NM_001257374.3:c.175A>G
NM_001282624.2:c.268A>G
NM_001282625.2:c.511A>G
NM_001282626.2:c.511A>G
NM_005572.4:c.511A>G
NM_170707.4:c.511A>GMANE SELECT
NM_170708.4:c.511A>G
NP_001244303.1:p.Lys59Glu
NP_001269553.1:p.Lys90Glu
NP_001269554.1:p.Lys171Glu
NP_001269555.1:p.Lys171Glu
NP_005563.1:p.Lys171Glu
NP_733821.1:p.Lys171Glu
NP_733822.1:p.Lys171Glu
LRG_254t2:c.511A>G
LRG_254:g.53199A>G
NC_000001.10:g.156100562A>G
NM_170707.2:c.511A>G

Protein change:

K171E

Links:

dbSNP: rs1650991296

NCBI 1000 Genomes Browser:

rs1650991296

Molecular consequence:

NM_001257374.3:c.175A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001282624.2:c.268A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001282625.2:c.511A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001282626.2:c.511A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_005572.4:c.511A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_170707.4:c.511A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_170708.4:c.511A>G - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004836719	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Jul 10, 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

SCV004836719

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Jul 10, 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	1	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, SCV004836719.1

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

Description

This missense variant replaces lysine with glutamic acid at codon 171 of the lamin A/C proteins. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). 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		1	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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