ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.6891+3G>T

gnomAD frequency: 0.00006  dbSNP: rs373333757
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000817173 SCV000957719 uncertain significance RYR1-related disorder 2022-06-27 criteria provided, single submitter clinical testing This sequence change falls in intron 42 of the RYR1 gene. It does not directly change the encoded amino acid sequence of the RYR1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs373333757, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with RYR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 660051). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
All of Us Research Program, National Institutes of Health RCV004001800 SCV004822270 uncertain significance Malignant hyperthermia, susceptibility to, 1 2023-10-02 criteria provided, single submitter clinical testing This variant causes a G to T nucleotide substitution at the +3 position of intron 42 of the RYR1 gene. To our knowledge, RNA studies have not been reported for this variant. This variant has not been reported in individuals affected with RYR1-related disorders in the literature. This variant has been identified in 6/280818 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
GenomeConnect - Invitae Patient Insights Network RCV003483740 SCV004228953 not provided Central core myopathy; Malignant hyperthermia, susceptibility to, 1; Congenital myopathy with fiber type disproportion; Multiminicore myopathy; Central core disease, autosomal recessive; Centronuclear myopathy no assertion provided phenotyping only Variant interpreted as Uncertain significance and reported on 01-10-2020 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

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