NM_170707.4(LMNA):c.448A>G (p.Thr150Ala) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 5, 2019
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:: RCV002327072.2

Allele description [Variation Report for NM_170707.4(LMNA):c.448A>G (p.Thr150Ala)]

NM_170707.4(LMNA):c.448A>G (p.Thr150Ala)

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.448A>G (p.Thr150Ala)

HGVS:

NC_000001.11:g.156130708A>G
NG_008692.2:g.53136A>G
NM_001257374.3:c.112A>G
NM_001282624.2:c.205A>G
NM_001282625.2:c.448A>G
NM_001282626.2:c.448A>G
NM_005572.4:c.448A>G
NM_170707.4:c.448A>GMANE SELECT
NM_170708.4:c.448A>G
NP_001244303.1:p.Thr38Ala
NP_001269553.1:p.Thr69Ala
NP_001269554.1:p.Thr150Ala
NP_001269554.1:p.Thr150Ala
NP_001269555.1:p.Thr150Ala
NP_005563.1:p.Thr150Ala
NP_733821.1:p.Thr150Ala
NP_733822.1:p.Thr150Ala
LRG_254t2:c.448A>G
LRG_254:g.53136A>G
NC_000001.10:g.156100499A>G
NM_001282625.1:c.448A>G
NM_170707.2:c.448A>G
NM_170707.3:c.448A>G

Protein change:

T150A

Links:

dbSNP: rs58917027

NCBI 1000 Genomes Browser:

rs58917027

Molecular consequence:

NM_001257374.3:c.112A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001282624.2:c.205A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001282625.2:c.448A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001282626.2:c.448A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_005572.4:c.448A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_170707.4:c.448A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_170708.4:c.448A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002635362	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Dec 5, 2019)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 10908904, 24037902, 24503780, 30287275 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002635362

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Dec 5, 2019)

germline

clinical testing

PubMed (4)
[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

Autosomal dominant Emery-Dreifuss dystrophy due to mutations in rod domain of the lamin A/C gene.

Felice KJ, Schwartz RC, Brown CA, Leicher CR, Grunnet ML.

Neurology. 2000 Jul 25;55(2):275-80.

PubMed [citation]

PMID:: 10908904

The genetics of dilated cardiomyopathy: a prioritized candidate gene study of LMNA, TNNT2, TCAP, and PLN.

Hirtle-Lewis M, Desbiens K, Ruel I, Rudzicz N, Genest J, Engert JC, Giannetti N.

Clin Cardiol. 2013 Oct;36(10):628-33. doi: 10.1002/clc.22193. Epub 2013 Aug 27.

PubMed [citation]

PMID:: 24037902
PMCID:: PMC6649360

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV002635362.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

The p.T150A variant (also known as c.448A>G), located in coding exon 2 of the LMNA gene, results from an A to G substitution at nucleotide position 448. The threonine at codon 150 is replaced by alanine, an amino acid with similar properties, and is located in the central rod domain. A different variant affecting this codon (p.T150P, c.448A>C) has been reported in association with Emery-Dreifuss muscular dystrophy with cardiac arrhythmia, and in a dilated cardiomyopathy (DCM) cohort (Felice KJ et al. Neurology, 2000 Jul;55:275-80; Pugh TJ et al. Genet. Med., 2014 Aug;16:601-8). An additional variant (p.T150I, c.449C>T) has also been reported in a DCM cohort (Hirtle-Lewis M et al. Clin Cardiol, 2013 Oct;36:628-33). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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: May 7, 2024

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