NM_170707.4(LMNA):c.618C>G (p.Phe206Leu) AND Cardiovascular phenotype

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 2, 2021
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:: RCV002354249.2

Allele description [Variation Report for NM_170707.4(LMNA):c.618C>G (p.Phe206Leu)]

NM_170707.4(LMNA):c.618C>G (p.Phe206Leu)

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.618C>G (p.Phe206Leu)

Other names:

p.F206L:TTC>TTG

HGVS:

NC_000001.11:g.156134507C>G
NG_008692.2:g.56935C>G
NM_001257374.3:c.282C>G
NM_001282624.2:c.375C>G
NM_001282625.2:c.618C>G
NM_001282626.2:c.618C>G
NM_005572.4:c.618C>G
NM_170707.4:c.618C>GMANE SELECT
NM_170708.4:c.618C>G
NP_001244303.1:p.Phe94Leu
NP_001269553.1:p.Phe125Leu
NP_001269553.1:p.Phe125Leu
NP_001269554.1:p.Phe206Leu
NP_001269555.1:p.Phe206Leu
NP_005563.1:p.Phe206Leu
NP_733821.1:p.Phe206Leu
NP_733822.1:p.Phe206Leu
LRG_254t2:c.618C>G
LRG_254:g.56935C>G
NC_000001.10:g.156104298C>G
NM_001282624.1:c.375C>G
NM_170707.2:c.618C>G
NM_170707.3:c.618C>G
P02545:p.Phe206Leu

Protein change:

F125L

Links:

UniProtKB: P02545#VAR_064964; dbSNP: rs267607629

NCBI 1000 Genomes Browser:

rs267607629

Molecular consequence:

NM_001257374.3:c.282C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001282624.2:c.375C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001282625.2:c.618C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001282626.2:c.618C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_005572.4:c.618C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_170707.4:c.618C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_170708.4:c.618C>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
SCV002657350	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Dec 2, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20848652, 26659599, 28663758 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002657350

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Dec 2, 2021)

germline

clinical testing

PubMed (3)
[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

Reproducible Analysis of Post-Translational Modifications in Proteomes--Application to Human Mutations.

Holehouse AS, Naegle KM.

PLoS One. 2015;10(12):e0144692. doi: 10.1371/journal.pone.0144692.

PubMed [citation]

PMID:: 26659599
PMCID:: PMC4685989

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV002657350.2

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

Description

The p.F206L pathogenic mutation (also known as c.618C>G), located in coding exon 3 of the LMNA gene, results from a C to G substitution at nucleotide position 618. The phenylalanine at codon 206 is replaced by leucine, an amino acid with highly similar properties. This variant has been detected in multiple individuals affected with laminopathy phenotypes, including limb-girdle muscular dystrophy (LGMD), dilated cardiomyopathy (DCM), and/or arrhythmias, and co-segregation has been reported in at least three families (Scharner J et al. Hum. Mutat., 2011 Feb;32:152-67; GeneDx pers comm; Invitae pers. comm.). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

#	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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