NM_170707.4(LMNA):c.1445G>A (p.Arg482Gln) AND Cardiomyopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 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:: RCV001179839.5

Allele description [Variation Report for NM_170707.4(LMNA):c.1445G>A (p.Arg482Gln)]

NM_170707.4(LMNA):c.1445G>A (p.Arg482Gln)

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.1445G>A (p.Arg482Gln)

HGVS:

NC_000001.11:g.156136985G>A
NG_008692.2:g.59413G>A
NM_001257374.3:c.1109G>A
NM_001282624.2:c.1202G>A
NM_001282625.2:c.1445G>A
NM_001282626.2:c.1445G>A
NM_005572.4:c.1445G>A
NM_170707.4:c.1445G>AMANE SELECT
NM_170708.4:c.1445G>A
NP_001244303.1:p.Arg370Gln
NP_001269553.1:p.Arg401Gln
NP_001269553.1:p.Arg401Gln
NP_001269554.1:p.Arg482Gln
NP_001269555.1:p.Arg482Gln
NP_005563.1:p.Arg482Gln
NP_733821.1:p.Arg482Gln
NP_733822.1:p.Arg482Gln
LRG_254t2:c.1445G>A
LRG_254:g.59413G>A
NC_000001.10:g.156106776G>A
NM_001257374.1:c.1109G>A
NM_001282624.1:c.1202G>A
NM_170707.2:c.1445G>A
NM_170707.3:c.1445G>A
NM_170707.3:c.[1445G>A]
P02545:p.Arg482Gln
c.1445G>A

Protein change:

R370Q; ARG482GLN

Links:

UniProtKB: P02545#VAR_009992; OMIM: 150330.0010; dbSNP: rs11575937

NCBI 1000 Genomes Browser:

rs11575937

Molecular consequence:

NM_001257374.3:c.1109G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282624.2:c.1202G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282625.2:c.1445G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282626.2:c.1445G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_005572.4:c.1445G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_170707.4:c.1445G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_170708.4:c.1445G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiomyopathy (CMYO)
Synonyms:: Cardiomyopathies
Identifiers:: MONDO: MONDO:0004994; MedGen: C0878544; Human Phenotype Ontology: HP:0001638

Recent activity

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acyl dehydratase [Hymenobacter sp. DG25B]
acyl dehydratase [Hymenobacter sp. DG25B]
gi|731476832|gnl|PRJNA266853|PK28_0 gb|AIZ63140.1|

Protein
Escherichia coli strain ED377 genome assembly, contig: scaffold_23, whole genome...
Escherichia coli strain ED377 genome assembly, contig: scaffold_23, whole genome shotgun sequence
gi|1052295689|emb|FBUZ01000024.1|

Nucleotide
Zea mays isolate 8112 clone 1 GRMZM2G383154-like gene, partial sequence
Zea mays isolate 8112 clone 1 GRMZM2G383154-like gene, partial sequence
gi|386650339|gb|JQ887437.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001344626	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Oct 5, 2023)	germline	clinical testing	PubMed (17) [See all records that cite these PMIDs] 10587585, 10999791, 19201734, 19418082, 19859838, 20130076, 20625965, 23313286, 26662654, 30165155, 31194872, 33803652, 34340952, 34865644, 35291351, 37679847, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001344626

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Oct 5, 2023)

germline

clinical testing

PubMed (17)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Nuclear lamin A/C R482Q mutation in canadian kindreds with Dunnigan-type familial partial lipodystrophy.

Cao H, Hegele RA.

Hum Mol Genet. 2000 Jan 1;9(1):109-12.

PubMed [citation]

PMID:: 10587585

LMNA R482Q mutation in partial lipodystrophy associated with reduced plasma leptin concentration.

Hegele RA, Cao H, Huff MW, Anderson CM.

J Clin Endocrinol Metab. 2000 Sep;85(9):3089-93.

PubMed [citation]

PMID:: 10999791

See all PubMed Citations (17)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001344626.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (17)

Description

This missense variant replaces arginine with glutamine at codon 482 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). This variant has been shown to cause partial lipodystrophy phenotype in a transgenic mouse model (PMID: 19201734). This variant has been reported in many individuals affected with familial partial lipodystrophy (PMID: 10587585, 10999791, 19418082, 19859838, 20130076, 20625965, 26662654, 30165155, 31194872, 33803652, 34340952, 34865644, 35291351, 37679847) and in individuals affected with Emery-Dreifuss muscular dystrophy (PMID: 23313286). However, this variant has not been reported in individuals affected with cardiomyopathy in the literature. This variant has been identified in 1/246132 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as a Variant of Uncertain Significance for autosomal dominant cardiomyopathy, although it is known to cause familial partial lipodystrophy (ClinVar variation ID: 14486).

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

Last Updated: Sep 16, 2024

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