ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.5115_5122del (p.Leu1706fs)

gnomAD frequency: 0.00001  dbSNP: rs1248355799
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000624873 SCV000740962 pathogenic Inborn genetic diseases 2015-07-07 criteria provided, single submitter clinical testing
GeneDx RCV003441972 SCV004167838 likely pathogenic not provided 2023-04-04 criteria provided, single submitter clinical testing Reported heterozygous in a neonate undergoing diagnostic exome sequencing; no specific clinical information provided (Powis et al., 2018); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 29565416)
All of Us Research Program, National Institutes of Health RCV004807047 SCV005431028 uncertain significance Malignant hyperthermia, susceptibility to, 1 2024-03-05 criteria provided, single submitter clinical testing This pathogenicity assessment is for autosomal dominant malignant hyperthermia susceptibility phenotype. This frameshift variant is predicted to result in an absent RYR1 protein product. Loss of RYR1 function due to haploinsufficiency is associated with congenital myopathy (https://clinicalgenome.org/), but it is not an established disease mechanism for autosomal dominant malignant hyperthermia susceptibility. Therefore, this variant is classified as a Variant of Uncertain Significance for malignant hyperthermia susceptibility.

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