Paediatric or syndromic cardiomyopathy

Gene: RPL3L

Green List (high evidence)

functional data is limited, but good genetic evidence (see papers above), ClinGen DCM expert panl group ahve recently rated as moderate gene for DCM, and onset is early

Created: 24 Feb 2026, 3:53 p.m. | Last Modified: 24 Feb 2026, 3:54 p.m.

Panel Version: 7.93

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Dilated Cardiomyopathy

Publications

• PMIDs: 8921388
• 32870709
• 35323613
• 32514796
• 36291431
• 37308880

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

Comment on list classification: There are now at least 14 individuals from 11 families with severe early-onset dilated cardiomyopathy. Almost all attributed to compound heterozygous missense variants (also 3 frameshift and 1 splice-site) but the underlying mechanism remains poorly understood. Notably, RPL3L knockout in mice did not result in any severe heart defects. (PMID: 32514796; 32870709; 36291431; 35323613; 37308880; 39803500; 40820268)

The number of cases reported supports inclusion on this panel as Green, but given that mouse models are conflicting and this addition was rejected in a previous GMS panel release, tagging for additional GMS expert review to determine the appropriate rating.

Created: 9 Oct 2025, 10:46 a.m. | Last Modified: 9 Oct 2025, 10:46 a.m.

Panel Version: 7.90

Comment on phenotypes: This gene now has a phenotype listed in OMIM: Cardiomyopathy, dilated, 2D, OMIM:619371 (accessed on 09-10-2025)

Created: 9 Oct 2025, 10:09 a.m. | Last Modified: 9 Oct 2025, 10:09 a.m.

Panel Version: 7.89

14 cases from 11 families have now been reported. Most variants are missense variants distributed across the entire gene, but 3 frameshift and a splice site variant have also been identified. RPL3L is specifically expressed in skeletal and cardiac muscles, and plays a role in myoblast fusion and myotube growth. However, the effect of RPL3L KO on cardiac function in mouse models are conflicting.

Created: 15 Sep 2025, 11 a.m. | Last Modified: 15 Sep 2025, 11 a.m.

Panel Version: 7.86

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neonatal dilated cardiomyopathy

Publications

• PMID: 40820268

Mode of pathogenicity
Other

After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed.

Created: 3 Mar 2022, 1:12 p.m. | Last Modified: 3 Mar 2022, 1:18 p.m.

Panel Version: 1.65

Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with any phenotypes in OMIM or Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.

Created: 16 Apr 2021, 8:24 a.m. | Last Modified: 16 Apr 2021, 8:24 a.m.

Panel Version: 1.26

Green List (high evidence)

PMID: 32514796 - 5 hom/chet individuals from three independent families who presented with severe neonatal dilated cardiomyopathy. Unaffected sibs were either carriers of a single variant or homozygous wildtype.
Sources: Literature

Created: 7 Jan 2021, 9:41 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neonatal dilated cardiomyopathy

Publications

• 32514796
• 32870709

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