ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.12536G>A (p.Arg4179His)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV005275013 SCV005936249 likely pathogenic Inborn genetic diseases 2025-03-03 criteria provided, single submitter clinical testing alThe c.12536G>A (p.R4179H) alteration is located in exon 90 (coding exon 90) of the RYR1 gene. This alteration results from a G to A substitution at nucleotide position 12536, causing the arginine (R) at amino acid position 4179 to be replaced by a histidine (H). for autosomal recessive RYR1-related myopathy; however, its clinical significance for autosomal dominant RYR1-related myopathy and autosomal dominant malignant hyperthermia susceptibility is uncertain. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant has been identified in conjunction with other RYR1 variants in individuals with features consistent with autosomal recessive RYR1-related myopathy; in at least one instance, the variants were identified in trans (Zhang, 2022; Garibaldi, 2019; Zhao, 2018; Bevilacqua, 2011). This amino acid position is highly conserved in available vertebrate species. This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as likely pathogenic.

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