RYR3 was first reported in relation to autosomal dominant developmental and epileptic encephalopathy in 2014 (EuroEPINOMICS-RES Consortium et al., PMID: 25262651). Of note, there is currently an additional assertion for autosomal recessive congenital myopathies resulting from biallelic RYR3 variants (OMIM: 620310). Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found differences in phenotype and inheritance pattern. Therefore, these assertions have been split into separate curations; the curation for autosomal recessive congenital myopathies has been completed by the ClinGen Congenital Myopathies GCEP. This curation only includes individuals with developmental and epileptic encephalopathy.
Two missense variants, reported in two probands in one publication are included in this curation (PMID: 25262651). Additional publications were reviewed, but no scorable evidence was identified. In summary, there is limited evidence to support the gene-disease relationship between RYR3 and autosomal dominant developmental and epileptic encephalopathy (MONDO:0100062). Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship.
This gene-disease pair was originally evaluated by the Epilepsy GCEP on June 19th, 2018. It was recurated on October 3rd, 2023. Several new papers were reviewed, but no new evidence was scored (PMIDs: 33557955, 29667327, 33994118). As a result of this reevaluation, the classification did not change.
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