Dilated and arrhythmogenic cardiomyopathy
Gene: RRAGD
After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Amber.Created: 30 Jan 2023, 2:04 p.m. | Last Modified: 30 Jan 2023, 2:04 p.m.
Panel Version: 2.4
Copied this gene from the Renal tubulopathies panel. In 6 cases reported in PMID: 34607910 (Schlingmann et al 2021) the probands also had dilated cardiomyopathy. The 6 patients with Dilated cardiomyopathy were diagnosed with the condition at ages between 6 months and 14 years old.Created: 2 Aug 2022, 10:53 p.m. | Last Modified: 14 Aug 2022, 9:11 p.m.
Panel Version: 1.28
Comment on list classification: Promoting from grey to amber but with a recommendation for GREEN rating following GMS review.Created: 2 Aug 2022, 10:35 p.m. | Last Modified: 2 Aug 2022, 10:35 p.m.
Panel Version: 2.62
Not associated with a phenotype in OMIM or Gene2Phenotype.
As reviewer states PMID: 34607910 (Schlingmann et al 2021) reports 8 cases where patients with hypomagnesaemia were found to have heterozygous (mostly de novo) missense variants in RRAGD. 6 patients also had dilated cardiomyopathy. In addition they report a family with a heterozygous variant in RRAGD that segregated with a kidney phenotype in eight members.Created: 2 Aug 2022, 10:34 p.m. | Last Modified: 14 Aug 2022, 9:11 p.m.
Panel Version: 1.28
publication from Nov 2021, reporting on 8 unrelated children with a phenotype of hypokalaemia, hypomagnesaemia and dilative cardiomyopathy who had mostly de novo heterozygous variants in RRAGD. Also identified a family where hypomagnesaemia segregated with a heterozygous variant in RRAGD in 8 members.
In vitro studies of variants are consistent with a gain-of-function, i.e. mTOR activation
Sources: LiteratureCreated: 7 Jul 2022, 9:23 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
hypomagnesaemia; cardiomyopathy
Publications
Mode of pathogenicity
Other
Tag Q3_22_rating was removed from gene: RRAGD.
Source NHS GMS was added to RRAGD.
Tag Q3_22_NHS_review was removed from gene: RRAGD.
gene: RRAGD was added gene: RRAGD was added to Dilated cardiomyopathy - adult and teen. Sources: Expert Review Amber,Literature Q3_22_rating, Q3_22_NHS_review tags were added to gene: RRAGD. Mode of inheritance for gene: RRAGD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RRAGD were set to 34607910 Phenotypes for gene: RRAGD were set to hypomagnesaemia; cardiomyopathy; tubular renal disease-cardiomyopathy syndrome, MONDO:0019130 Penetrance for gene: RRAGD were set to Complete Mode of pathogenicity for gene: RRAGD was set to Other