NM_170707.4(LMNA):c.448A>C (p.Thr150Pro) AND Primary dilated cardiomyopathy

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 15, 2012
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:: RCV000041350.5

Allele description [Variation Report for NM_170707.4(LMNA):c.448A>C (p.Thr150Pro)]

NM_170707.4(LMNA):c.448A>C (p.Thr150Pro)

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>C (p.Thr150Pro)

HGVS:

NC_000001.11:g.156130708A>C
NG_008692.2:g.53136A>C
NM_001257374.3:c.112A>C
NM_001282624.2:c.205A>C
NM_001282625.2:c.448A>C
NM_001282626.2:c.448A>C
NM_005572.4:c.448A>C
NM_170707.4:c.448A>CMANE SELECT
NM_170708.4:c.448A>C
NP_001244303.1:p.Thr38Pro
NP_001269553.1:p.Thr69Pro
NP_001269554.1:p.Thr150Pro
NP_001269555.1:p.Thr150Pro
NP_005563.1:p.Thr150Pro
NP_733821.1:p.Thr150Pro
NP_733822.1:p.Thr150Pro
LRG_254t1:c.448A>C
LRG_254t2:c.448A>C
LRG_254:g.53136A>C
NC_000001.10:g.156100499A>C
NM_005572.3:c.448A>C
NM_170707.2:c.448A>C
P02545:p.Thr150Pro
c.448A>C

Protein change:

T150P

Links:

UniProtKB: P02545#VAR_039762; dbSNP: rs58917027

NCBI 1000 Genomes Browser:

rs58917027

Molecular consequence:

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000065043	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Likely pathogenic (Mar 15, 2012)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 10908904, 20848652, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000065043

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Likely pathogenic
(Mar 15, 2012)

germline

clinical testing

PubMed (3)
[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	not provided	4	1	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

Novel LMNA mutations in patients with Emery-Dreifuss muscular dystrophy and functional characterization of four LMNA mutations.

Scharner J, Brown CA, Bower M, Iannaccone ST, Khatri IA, Escolar D, Gordon E, Felice K, Crowe CA, Grosmann C, Meriggioli MN, Asamoah A, Gordon O, Gnocchi VF, Ellis JA, Mendell JR, Zammit PS.

Hum Mutat. 2011 Feb;32(2):152-67. doi: 10.1002/humu.21361. Epub 2011 Jan 25.

PubMed [citation]

PMID:: 20848652

See all PubMed Citations (3)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000065043.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	4	not provided	not provided	clinical testing	PubMed (3)

Description

The Thr150Pro variant (LMNA) has been previously reported in 2 individuals with Emery-Dreifuss muscular dystrophy who also had conduction system disease and was absent from 160 control chromosomes (Felice 2000, Schamer 2011). Our laboratory has identified this variant in 1 out over >500 Caucasian probands with cardiomy opathy. The variant was present in 4 affected family members, supporting a patho genic role. Consistent with a laminopathy, clinical features in this family incl ude DCM, muscle weakness and conduction system disease. Threonine (Thr) at posit ion conserved in mammals, frog, and fish (lower species not available), which su ggests that a change may not be tolerated. Computational tools (AlignGVGD and SI FT) also support a pathogenic role, though their accuracy is unknown. In summary , this variant is considered to be likely pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		4	not provided	1	not provided

Last Updated: Apr 6, 2024

ClinVar

Relating variation to medicine