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NM_170707.4(LMNA):c.1445G>A (p.Arg482Gln) AND LMNA-related disorder

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 7, 2024
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV004532361.2

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:
LMNA-related disorder
Synonyms:
LMNA-Related Disorders; LMNA-related condition; LMNA-related disease
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004121213PreventionGenetics, part of Exact Sciences
no assertion criteria provided
Pathogenic
(Aug 7, 2024) 		germlineclinical testing

Help

Summary from all submissions

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

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004121213.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The LMNA c.1445G>A variant is predicted to result in the amino acid substitution p.Arg482Gln. This variant has been reported in the homozygous state in two Hutterite siblings that presented with an atypical Emery-Dreifuss muscular dystrophy and in the heterozygous state in other family members with familial partial lipodystrophy and abnormal lipid profiles (Wiltshire et al. 2013. PMID: 23313286). Of note, the authors tested for the c.1445G>A variant in 482 Dariusleut and Leherleut Hutterites in Alberta and found the overall carrier frequency to be 1.45%. In addition, this variant in the heterozygous state has been reported in several unrelated families of other ethnicities to be causative for familial partial lipodystrophy in an autosomal dominant manner (Cao and Hegele. 2000. PubMed ID: 10587585; Hegele et al. 2000. PubMed ID: 10999791; Speckman et al. 2000. PubMed ID: 10739751; Vasandani et al. 2022. PubMed ID: 36397776; http://www.LOVD.nl/LMNA). This variant has not been reported in a large population database, indicating this variant is rare. In summary, the c.1445G>A variant is pathogenic for a spectrum of laminopathies in both the heterozygous and homozygous state.

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

Last Updated: Oct 20, 2024