NM_007078.3(LDB3):c.1487T>C (p.Phe496Ser) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 7, 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:: RCV002390470.8

Allele description [Variation Report for NM_007078.3(LDB3):c.1487T>C (p.Phe496Ser)]

NM_007078.3(LDB3):c.1487T>C (p.Phe496Ser)

Gene:

LDB3:LIM domain binding 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q23.2

Genomic location:

Preferred name:

NM_007078.3(LDB3):c.1487T>C (p.Phe496Ser)

Other names:

p.F496S:TTC>TCC

HGVS:

NC_000010.11:g.86716582T>C
NG_008876.1:g.53019T>C
NM_001080114.2:c.1157T>C
NM_001171610.2:c.1502T>C
NM_001368064.1:c.1298T>C
NM_001368065.1:c.1298T>C
NM_001368066.1:c.1346T>C
NM_007078.3:c.1487T>CMANE SELECT
NP_001073583.1:p.Phe386Ser
NP_001165081.1:p.Phe501Ser
NP_001354993.1:p.Phe433Ser
NP_001354994.1:p.Phe433Ser
NP_001354995.1:p.Phe449Ser
NP_009009.1:p.Phe496Ser
NP_009009.1:p.Phe496Ser
LRG_385t1:c.1487T>C
LRG_385:g.53019T>C
LRG_385p1:p.Phe496Ser
NC_000010.10:g.88476339T>C
NM_001080115.1:c.*17208T>C
NM_001171610.1:c.1502T>C
NM_007078.2:c.1487T>C

Protein change:

F386S

Links:

dbSNP: rs147072071

NCBI 1000 Genomes Browser:

rs147072071

Molecular consequence:

NM_001080114.2:c.1157T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001171610.2:c.1502T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001368064.1:c.1298T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001368065.1:c.1298T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001368066.1:c.1346T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_007078.3:c.1487T>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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
SCV002698592	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Uncertain significance (Apr 7, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29247119, 30847666 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002698592

Ambry Genetics

criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)

Uncertain significance
(Apr 7, 2021)

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	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Applying High-Resolution Variant Classification to Cardiac Arrhythmogenic Gene Testing in a Demographically Diverse Cohort of Sudden Unexplained Deaths.

Lin Y, Williams N, Wang D, Coetzee W, Zhou B, Eng LS, Um SY, Bao R, Devinsky O, McDonald TV, Sampson BA, Tang Y.

Circ Cardiovasc Genet. 2017 Dec;10(6). doi:pii: e001839. 10.1161/CIRCGENETICS.117.001839.

PubMed [citation]

PMID:: 29247119

Large next-generation sequencing gene panels in genetic heart disease: yield of pathogenic variants and variants of unknown significance.

van Lint FHM, Mook ORF, Alders M, Bikker H, Lekanne Dit Deprez RH, Christiaans I.

Neth Heart J. 2019 Jun;27(6):304-309. doi: 10.1007/s12471-019-1250-5.

PubMed [citation]

PMID:: 30847666
PMCID:: PMC6533346

Details of each submission

From Ambry Genetics, SCV002698592.1

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

Description

The p.F496S variant (also known as c.1487T>C), located in coding exon 9 of the LDB3 gene, results from a T to C substitution at nucleotide position 1487. The phenylalanine at codon 496 is replaced by serine, an amino acid with highly dissimilar properties. This variant (also described as p.F386S) has been reported in a sudden unexplained death case and a dilated cardiomyopathy genetic testing case; however, clinical details were limited for both individuals (Lin Y et al. Circ Cardiovasc Genet, 2017 Dec;10:[Epub ahead of print]; van Lint FHM et al. Neth Heart J, 2019 Jun;27:304-309).This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated 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	1	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Apr 20, 2024

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