Paediatric or syndromic cardiomyopathy

Gene: KBTBD13

I don't know

Comment on list classification: Although three unrelated families and evidence from mouse model are available in support of the association, all cases were reported with the same founder variant. Hence, this gene should be rated amber with the current evidence.

Created: 14 Nov 2024, 3:17 p.m. | Last Modified: 14 Nov 2024, 3:17 p.m.

Panel Version: 6.3

As reviewed by Dmitrijs Rots, PMID:36335629 reported a cardiac phenotype in three unrelated families with Nemaline myopathy (MIM #609273) and the Dutch founder variant, p.Arg408Cys. A total of 65 NEM6 patients were evaluated, of whom 12% presented with left ventricle dilatation, 29% with left ventricular ejection fraction< 50%, 8% with atrial fibrillation, 9% with ventricular tachycardia, and 20% with repolarization abnormalities. Five patients received an implantable cardioverter defibrillator, three cases of sudden cardiac death were reported. Linkage analysis confirmed cosegregation of the KBTBD13 p.Arg408Cys variant with the cardiac phenotype. Evidence from mouse models also confirmed cardiac dysfunction.

Created: 14 Nov 2024, 3:12 p.m. | Last Modified: 14 Nov 2024, 3:12 p.m.

Panel Version: 6.1

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Nemaline myopathy 6, autosomal dominant, OMIM:609273; intrinsic cardiomyopathy, MONDO:0000591

Publications

• 36335629

Green List (high evidence)

3 families with cardiomyopathy and other related cardiac phenotypes reported in 36335629 with mouse model. Enough evidence for green. All cases had p.R408C variant.
Sources: Literature

Created: 14 Dec 2022, 9:30 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Publications

• 36335629

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments