Mosaic brain disorders - deep sequencing

Gene: RPS6

The rating of this gene has been updated to Red and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.

Created: 11 Oct 2023, 8:53 a.m. | Last Modified: 11 Oct 2023, 8:53 a.m.

Panel Version: 0.133

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

Red List (low evidence)

Either rate red or remove please

Created: 31 May 2023, 9:33 a.m. | Last Modified: 31 May 2023, 9:33 a.m.

Panel Version: 0.100

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Hemimegalencephaly with intractable epilepsy

Publications

• PMID: 31411685

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

Comment on list classification: Only a single patient has been reported to date who harboured a somatic mosaic missense VUS (c.695G > A; p.R232H) in the RPS6 gene. A concurrent somatic mosaic missense variant (c.6644C > T; p.S2215F) was identified in the MTOR gene. Authors speculated that it was this combination of variants affecting the mTOR pathway that contributed to the patients phenotype as demonstrated by a more severe phenotype in double mutant rats.

This gene is not associated with any phenotypes in OMIM, G2P or other PanelApp panels.

Recommending Red rating, awaiting further cases that would corroborate this association.

Created: 22 Dec 2022, 12:12 p.m. | Last Modified: 22 Dec 2022, 12:12 p.m.

Panel Version: 0.62

Red List (low evidence)

The rating of this gene has been updated to Red and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.

Created: 1 Feb 2023, 5:26 p.m. | Last Modified: 1 Feb 2023, 5:38 p.m.

Panel Version: 0.93

Review submitted on behalf of Dr Lara Menzies, Dr Wendy Jones, Dr Amy McTague. Mode of inheritance: mosaic. Publications: Pelorusso et al 2019 Human Molecular Genetics. Mechanism: no information provided. Penetrance: no information provided.

Created: 21 Dec 2022, 12:16 p.m. | Last Modified: 21 Dec 2022, 12:16 p.m.

Panel Version: 0.2

Phenotypes
Hemimegalencephaly with intractable epilepsy