Dilated Cardiomyopathy and conduction defects

Gene: LDB3

Amber List (moderate evidence)

LDB3 (LIM domain binding 3)
EnsemblGeneIds (GRCh38): ENSG00000122367
EnsemblGeneIds (GRCh37): ENSG00000122367
OMIM: 605906, Gene2Phenotype
LDB3 is in 16 panels

6 reviews

Ivone Leong (Genomics England Curator)

Comment on list classification: Demoted from Green to Amber. This gene is associated with a phenotype in OMIM and Gene2Phenotype (requires clinical review). However, based on the expert reviews there is not enough evidence to support a gene-disease association. Therefore this gene has been given an Amber rating.
Created: 15 Mar 2022, 8:42 a.m. | Last Modified: 15 Mar 2022, 8:42 a.m.
Panel Version: 1.77
Comment on publications: Added new publications
Created: 15 Mar 2022, 8:36 a.m. | Last Modified: 15 Mar 2022, 8:36 a.m.
Panel Version: 1.76

Matthew Edwards (Clinical Genetics & Genomics Lab, Royal Brompton & Harefield NHS Trust)

I don't know

Some missense variants reported in humans (but gene is not constrained for missense varation), and some experimental evidence for gene-disease association. Very limited segregation with an LVNC/DCMphenotype for c.2032G>A (PMID: 14660611), but this is common enough in controls to be unlikely causative of monogenic disease, even with reduced penetrance. ClinGen rates as limited evidence for DCM. This gene should be amber at best for a DCM panel
Created: 14 Mar 2022, 10:53 a.m. | Last Modified: 14 Mar 2022, 10:53 a.m.
Panel Version: 1.75

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Cardiomyopathy, dilated, 1C, with or without LVNC (OMIM #601493)

Publications

Rebecca Whittington (South West GLH)

I don't know

Cardiomyopathy, dilated, 1C, with or without LVNC OMIM#601493; Cardiomyopathy, hypertrophic, 24 OMIM#601493; Left ventricular noncompaction 3 OMIM#601493; Myopathy, myofibrillar, 4 OMIM#609452.
Created: 25 Mar 2019, 4:30 p.m.
HGMD: Four variants assoc with DCM - only one DM. Haas 2015 lists 2 as VUS. Included in review of DCM genes: Dalin 2017 International Journal of Cardiology 228 (2017) 742748, Hershberger 2013 Nat Rev Cardiol 10:531.
Created: 25 Mar 2019, 4:27 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Variants in this GENE are reported as part of current diagnostic practice

Ellen McDonagh (Genomics England Curator)

I don't know

This gene was part of an initial gene list collated by Matthew Edwards Royal Brompton Hospital sent 16th Jan 2019 on behalf of the London South GLH for review by the GMS Cardiology Specialist Group. Only gene symbol from the Royal Brompton gene panel was provided - suggested initial gene rating and evidence for inclusion not provided with the list.
Created: 20 Feb 2019, 2:17 p.m.

Caroline Wright (Genomics England Curator)

Comment when marking as ready: Lots of unrelated patients in OMIM; on DDG2P linked to DCM
Created: 14 Feb 2016, 4:18 p.m.

Oxford Medical Genetics Laboratory (OUH NHS Foundation Trust)

Red List (low evidence)

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
  • South West GLH
  • London South GLH
  • Expert list
  • Emory Genetics Laboratory
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • Cardiomyopathy, dilated 1C
OMIM
605906
Clinvar variants
Variants in LDB3
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

15 Mar 2022, Gel status: 2

Entity classified by Genomics England curator

Ivone Leong (Genomics England Curator)

Gene: ldb3 has been classified as Amber List (Moderate Evidence).

15 Mar 2022, Gel status: 3

Set publications

Ivone Leong (Genomics England Curator)

Publications for gene: LDB3 were set to

21 Feb 2019, Gel status: 4

Added New Source, Set mode of inheritance

Ellen McDonagh (Genomics England Curator)

Source South West GLH was added to LDB3. Mode of inheritance for gene LDB3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

20 Feb 2019, Gel status: 3

Added New Source, Status Update

Ellen McDonagh (Genomics England Curator)

Source London South GLH was added to LDB3. Rating Changed from Green List (high evidence) to Green List (high evidence)

14 Feb 2016, Gel status: 4

Gene classified by Genomics England curator

Caroline Wright (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

14 Jul 2015, Gel status: 3

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene LDB3 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

14 Jul 2015, Gel status: 3

Added New Source

Ellen McDonagh (Genomics England Curator)

LDB3 was added to Dilated Cardiomyopathy and conduction defectspanel. Sources: Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,Expert list

14 Jul 2015, Gel status: 3

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene LDB3 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

14 Jul 2015, Gel status: 3

Added New Source

Ellen McDonagh (Genomics England Curator)

LDB3 was added to Dilated Cardiomyopathy and conduction defectspanel. Sources: Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,Expert list

14 Jul 2015, Gel status: 2

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene LDB3 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

14 Jul 2015, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

LDB3 was added to Dilated Cardiomyopathy and conduction defectspanel. Sources: Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,Expert list

14 Jul 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

LDB3 was added to Dilated Cardiomyopathy and conduction defectspanel. Sources: Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,Expert list