NM_170707.4(LMNA):c.883T>C (p.Ser295Pro) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 2, 2017
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:: RCV002444515.2

Allele description [Variation Report for NM_170707.4(LMNA):c.883T>C (p.Ser295Pro)]

NM_170707.4(LMNA):c.883T>C (p.Ser295Pro)

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.883T>C (p.Ser295Pro)

HGVS:

NC_000001.11:g.156135259T>C
NG_008692.2:g.57687T>C
NM_001257374.3:c.547T>C
NM_001282624.2:c.640T>C
NM_001282625.2:c.883T>C
NM_001282626.2:c.883T>C
NM_005572.4:c.883T>C
NM_170707.3:c.883T>C
NM_170707.4:c.883T>CMANE SELECT
NM_170708.4:c.883T>C
NP_001244303.1:p.Ser183Pro
NP_001269553.1:p.Ser214Pro
NP_001269554.1:p.Ser295Pro
NP_001269555.1:p.Ser295Pro
NP_005563.1:p.Ser295Pro
NP_733821.1:p.Ser295Pro
NP_733822.1:p.Ser295Pro
LRG_254t2:c.883T>C
LRG_254:g.57687T>C
NC_000001.10:g.156105050T>C
NM_170707.2:c.883T>C
P02545:p.Ser295Pro

Protein change:

S183P

Links:

UniProtKB: P02545#VAR_064967; dbSNP: rs267607633

NCBI 1000 Genomes Browser:

rs267607633

Molecular consequence:

NM_001257374.3:c.547T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001282624.2:c.640T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001282625.2:c.883T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001282626.2:c.883T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_005572.4:c.883T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_170707.4:c.883T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_170708.4:c.883T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

Recent activity

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88224398[uid] AND (alive[prop]) (1)
Gene
MCA_RS10675 [Methylococcus capsulatus str. Bath]
MCA_RS10675 [Methylococcus capsulatus str. Bath]
Gene ID:88224398

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002682726	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Mar 2, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 20848652, 25832542 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002682726

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Mar 2, 2017)

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

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

Ameliorating pathogenesis by removing an exon containing a missense mutation: a potential exon-skipping therapy for laminopathies.

Scharner J, Figeac N, Ellis JA, Zammit PS.

Gene Ther. 2015 Jun;22(6):503-15. doi: 10.1038/gt.2015.8. Epub 2015 Apr 2.

PubMed [citation]

PMID:: 25832542

Details of each submission

From Ambry Genetics, SCV002682726.2

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

Description

The p.S295P variant (also known as c.883T>C), located in coding exon 5 of the LMNA gene, results from a T to C substitution at nucleotide position 883. The serine at codon 295 is replaced by proline, an amino acid with similar properties, and is located in the coil 2 domain. This alteration has been reported in a single individual with muscular dystrophy and cardiomyopathy with conduction disease (Scharner J et al. Hum. Mutat., 2011 Feb;32:152-67). This variant alters nuclear morphology as well as Lamin A and Lamin B1/emerin distribution (Scharner J et al. Gene Ther., 2015 Jun;22:503-15). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. 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 1, 2024

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