Hypertrophic cardiomyopathy

Gene: RPS6KB1

After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber. The reviewers felt there was not yet sufficient evidence for a gene-disease association and there is a 'limited' rating for this association in ClinGen (as of 13-Sept-2023).

Created: 6 Dec 2024, 6:49 p.m. | Last Modified: 6 Dec 2024, 6:52 p.m.

Panel Version: 4.19

Green List (high evidence)

Comment on list classification: This gene should be promoted to Green at the next GMS panel update (5 unrelated cases plus functional data)

Created: 9 Nov 2022, 5:19 p.m. | Last Modified: 9 Nov 2022, 5:19 p.m.

Panel Version: 2.44

Jain et al. 2022 (PMID: 34916228) reported on two unrelated HCM families with the same heterozygous missense RPS6KB1 variant (p.G47W), and subsequently three further unrelated probands with HCM harbouring distinct heterozygous variants (p.Q49K, p.Y62H, respectively). Variants segregated with disease, were predicted pathogenic by silico analyses and were ultrarare or absent in population databases. Functional studies in the HL-1 (mouse cardiomyocytes) cells showed that the patient-specific RPS6KB1 mutant significantly increased cell size and activated rpS6 and ERK1/2 signalling cascades. The relationship between RPS6KB1 and cardiac hypertrophy has also been explored in feline and mice models (PMID: 15226426; 17976640)
Sources: Literature

Created: 9 Nov 2022, 5:17 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Hypertrophic cardiomyopathy

Publications

• 34916228