ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.1007_1008del (p.Pro336fs)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Breakthrough Genomics, Breakthrough Genomics RCV004596704 SCV005088871 likely pathogenic Congenital multicore myopathy with external ophthalmoplegia 2021-01-15 criteria provided, single submitter clinical testing This variant is predicted to cause a frameshift and consequent premature termination of the protein (p.Pro336ArgfsTer168) and the resultant protein will likely to lack SPRY domains, EF-hand domain and transmembrane domain of the protein [UniProt]; this will likely result in loss-of-function. Due to the introduction of a premature stop codon, this aberrant transcript will likely be targeted by the nonsense-mediated mRNA decay (NMD) mechanism [PMID: 15040442]. The variant seems to be a novel variant, as it has not been previously reported in population databases or in the literature. However, several other truncating variants lying downstream of the identified variant, has been previously reported as ‘pathogenic’ in the ClinVar database context of RYR1-related disorders. In addition, loss-of-function variants in RYR1 are known to be pathogenic [PMID: 20583297, 23919265].

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