NM_170707.4(LMNA):c.83G>A (p.Arg28Gln) AND Emery-Dreifuss muscular dystrophy 2, autosomal dominant

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Sep 29, 2022
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:: RCV002298563.1

Allele description [Variation Report for NM_170707.4(LMNA):c.83G>A (p.Arg28Gln)]

NM_170707.4(LMNA):c.83G>A (p.Arg28Gln)

Genes:

LOC129931597:ATAC-STARR-seq lymphoblastoid silent region 1421 [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.83G>A (p.Arg28Gln)

HGVS:

NC_000001.11:g.156115001G>A
NG_008692.2:g.37429G>A
NM_001282625.2:c.83G>A
NM_001282626.2:c.83G>A
NM_005572.4:c.83G>A
NM_170707.4:c.83G>AMANE SELECT
NM_170708.4:c.83G>A
NP_001269554.1:p.Arg28Gln
NP_001269555.1:p.Arg28Gln
NP_005563.1:p.Arg28Gln
NP_733821.1:p.Arg28Gln
NP_733822.1:p.Arg28Gln
LRG_254:g.37429G>A
NC_000001.10:g.156084792G>A
NM_170707.3:c.83G>A

Protein change:

R28Q

Links:

dbSNP: rs886043109

NCBI 1000 Genomes Browser:

rs886043109

Molecular consequence:

NM_001282625.2:c.83G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282626.2:c.83G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_005572.4:c.83G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_170707.4:c.83G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_170708.4:c.83G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Emery-Dreifuss muscular dystrophy 2, autosomal dominant (EDMD2)
Synonyms:: MUSCULAR DYSTROPHY WITH EARLY CONTRACTURES AND CARDIOMYOPATHY, AUTOSOMAL DOMINANT; SCAPULOILIOPERONEAL ATROPHY WITH CARDIOPATHY; Benign scapuloperoneal muscular dystrophy with cardiomyopathy; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0021569; MedGen: C0410190; Orphanet: 261; Orphanet: 264; OMIM: 181350

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002599027	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Sep 29, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 21632249, 20980393 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002599027

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Sep 29, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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

Inflammatory changes in infantile-onset LMNA-associated myopathy.

Komaki H, Hayashi YK, Tsuburaya R, Sugie K, Kato M, Nagai T, Imataka G, Suzuki S, Saitoh S, Asahina N, Honke K, Higuchi Y, Sakuma H, Saito Y, Nakagawa E, Sugai K, Sasaki M, Nonaka I, Nishino I.

Neuromuscul Disord. 2011 Aug;21(8):563-8. doi: 10.1016/j.nmd.2011.04.010. Epub 2011 May 31.

PubMed [citation]

PMID:: 21632249

Specific phosphorylation of Ser458 of A-type lamins in LMNA-associated myopathy patients.

Mitsuhashi H, Hayashi YK, Matsuda C, Noguchi S, Wakatsuki S, Araki T, Nishino I.

J Cell Sci. 2010 Nov 15;123(Pt 22):3893-900. doi: 10.1242/jcs.072157. Epub 2010 Oct 27.

PubMed [citation]

PMID:: 20980393

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002599027.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: LMNA c.83G>A (p.Arg28Gln) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 223856 control chromosomes (gnomAD). c.83G>A has been reported in the literature in an individual diagnosed with limb-girdle muscular dystrophy, type 1B and in an individual affected with inflammatory myopathy (e.g. Mitsuhashi_2010, Komaki_2011). Other variants affecting the same amino acid residue (p.Arg28Gly, p.Arg28Trp) are cited in ClinVar and HGMD as pathogenic and disease-associated. These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.

#	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: Mar 16, 2024

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