Fetal anomalies
Gene: LDB3

LDB3 (LIM domain binding 3)
EnsemblGeneIds (GRCh38): ENSG00000122367
EnsemblGeneIds (GRCh37): ENSG00000122367
OMIM: 605906, Gene2Phenotype
LDB3 is in 14 panels

3 reviews

Arina Puzriakova (Genomics England Curator)

This gene and phenotype were reviewed during meetings between November 2025 & January 2026. The meetings included representatives of the Central & South and North Thames R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Stephanie Allen, Elizabeth Young and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Tazeen Ashraf, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Tessa Homfray, Esther Kinning, and Soo-Mi Park (R21 Clinical Oversight Group).
Created: 10 Mar 2026, 11:35 a.m. | Last Modified: 10 Mar 2026, 11:35 a.m.

Panel Version: 6.148

Created: 10 Mar 2026, 11:35 a.m.
Last Modified: 10 Mar 2026, 11:35 a.m.
Panel version: 6.148

Beth Young (West Midlands Regional Genetics Laboratory)

I don't know

Currently red on FA panel following downgraded in April 2019. Note from that review; Concluded that myopathy is unlikely to produce Fetal hydrops in this instance. Although PMID:17394203 report a proband with variants in both TAZ and LDB3, where the mother had five miscarriages (plus two sons who died in infancy and 2 surviving children) the LDB3 variant is paternally-inherited, and therefore the maternally-inherited TAZ allele is more relevant. Action taken: Demoted LDB3 gene rating from Amber to Red. Koopman et al 2023 (PMID 36253531) report 5 unrelated families with biallelic variants and severe, early onset DCM. ONe family had a prenatal phenotype that included bilateral talipes and cardiomegaly (normal structurally). Exome sequencing identified biparentally inherited Likely Path variants in LDB3 and no other variants of concern. Post mortem examination showed mild wrist contractures and hypertrophic left ventricle.
Created: 10 Mar 2026, 11:27 a.m. | Last Modified: 10 Mar 2026, 11:27 a.m.

Panel Version: 6.147

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Dilated cardiomyopathy

Publications

36253531

Created: 10 Mar 2026, 11:27 a.m.
Last Modified: 10 Mar 2026, 11:27 a.m.
Panel version: 6.147

Rebecca Foulger (Genomics England curator)

Red List (low evidence)

This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March and April 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Originally rated Amber based on DDG2P Disease confidence of 'both DD and IF' for at least one disorder. Outcome of review: Phenotype is not fetally-relevant. Additional notes from clinical review: Concluded that myopathy is unlikely to produce Fetal hydrops in this instance. Although PMID:17394203 report a proband with variants in both TAZ and LDB3, where the mother had five miscarriages (plus two sons who died in infancy and 2 surviving children) the LDB3 variant is paternally-inherited, and therefore the maternally-inherited TAZ allele is more relevant. Action taken: Demoted LDB3 gene rating from Amber to Red.
Created: 29 Apr 2019, 12:28 p.m.

Changed rating to Amber to reflect DDG2P Disease confidence of 'DD and IF' for LEFT VENTRICULAR NON-COMPACTION TYPE 3; CARDIOMYOPATHY DILATED TYPE 1C; MYOPATHY MYOFIBRILLAR TYPE 4.
Created: 12 Feb 2019, 2:32 p.m.

Rating in original PAGE file: 'both DD and IF' for LEFT VENTRICULAR NON-COMPACTION TYPE 3 and CARDIOMYOPATHY DILATED TYPE 1C and MYOPATHY MYOFIBRILLAR TYPE 4.
Created: 6 Dec 2018, 10:07 a.m.

In the original PAGE file, MOP listed as All missense/in frame for all disorders.
Created: 8 Nov 2018, 4:45 p.m.

Publications

17394203

Mode of pathogenicity
Other - please provide details in the comments

Created: 8 Nov 2018, 4:45 p.m.

Panel version: 0.222

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Amber
PAGE DD-Gene2Phenotype

Phenotypes

MYOPATHY MYOFIBRILLAR TYPE 4
LEFT VENTRICULAR NON-COMPACTION TYPE 3
Dilated cardiomyopathy
CARDIOMYOPATHY DILATED TYPE 1C

OMIM

605906

Clinvar variants

Variants in LDB3

Penetrance

None

Publications

17394203

Panels with this gene

History Filter Activity

10 Mar 2026, Gel status: 2

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Added phenotypes Dilated cardiomyopathy for gene: LDB3

9 Mar 2026, Gel status: 2

Added New Source, Set mode of inheritance, Status Update

Arina Puzriakova (Genomics England Curator)

Source Expert Review Amber was added to LDB3. Mode of inheritance for gene LDB3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal Rating Changed from Red List (low evidence) to Amber List (moderate evidence)

29 Apr 2019, Gel status: 1