NM_170707.4(LMNA):c.1184C>T (p.Ser395Leu) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 17, 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:: RCV002336206.2

Allele description [Variation Report for NM_170707.4(LMNA):c.1184C>T (p.Ser395Leu)]

NM_170707.4(LMNA):c.1184C>T (p.Ser395Leu)

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.1184C>T (p.Ser395Leu)

HGVS:

NC_000001.11:g.156136240C>T
NG_008692.2:g.58668C>T
NM_001257374.3:c.848C>T
NM_001282624.2:c.941C>T
NM_001282625.2:c.1184C>T
NM_001282626.2:c.1184C>T
NM_005572.4:c.1184C>T
NM_170707.4:c.1184C>TMANE SELECT
NM_170708.4:c.1184C>T
NP_001244303.1:p.Ser283Leu
NP_001269553.1:p.Ser314Leu
NP_001269554.1:p.Ser395Leu
NP_001269555.1:p.Ser395Leu
NP_005563.1:p.Ser395Leu
NP_733821.1:p.Ser395Leu
NP_733822.1:p.Ser395Leu
LRG_254t2:c.1184C>T
LRG_254:g.58668C>T
NC_000001.10:g.156106031C>T
NM_170707.2:c.1184C>T
NM_170707.3:c.1184C>T

Protein change:

S283L

Links:

dbSNP: rs267607561

NCBI 1000 Genomes Browser:

rs267607561

Molecular consequence:

NM_001257374.3:c.848C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001282624.2:c.941C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001282625.2:c.1184C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001282626.2:c.1184C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_005572.4:c.1184C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_170707.4:c.1184C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_170708.4:c.1184C>T - 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
SCV002635720	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Sep 17, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002635720

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Sep 17, 2019)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

New metabolic phenotypes in laminopathies: LMNA mutations in patients with severe metabolic syndrome.

Decaudain A, Vantyghem MC, Guerci B, Hécart AC, Auclair M, Reznik Y, Narbonne H, Ducluzeau PH, Donadille B, Lebbé C, Béréziat V, Capeau J, Lascols O, Vigouroux C.

J Clin Endocrinol Metab. 2007 Dec;92(12):4835-44. Epub 2007 Aug 21.

PubMed [citation]

PMID:: 17711925

Details of each submission

From Ambry Genetics, SCV002635720.2

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

Description

The p.S395L variant (also known as c.1184C>T), located in coding exon 7 of the LMNA gene, results from a C to T substitution at nucleotide position 1184. The serine at codon 395 is replaced by leucine, an amino acid with dissimilar properties. This variant was observed in one 60 year old patient with metabolic syndrome, coronary heart disease, atherosclerois, hypertension, insulin-resistant diabetes and related complications including retinopathy, nephropathy, and peripheral neuropathy. However, he lacked clinical lipodystrophy and any muscular symptoms (Decaudain A et al. J. Clin. Endocrinol. Metab., 2007 Dec;92:4835-44). This amino acid position is 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: Sep 29, 2024

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