Submissions for variant NM_000540.3(RYR1):c.14970-5C>G

gnomAD frequency: 0.00002  dbSNP: rs527738921

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002050656	SCV002115372	uncertain significance	RYR1-related disorder	2024-12-18	criteria provided, single submitter	clinical testing	This sequence change falls in intron 104 of the RYR1 gene. It does not directly change the encoded amino acid sequence of the RYR1 protein. This variant is present in population databases (rs527738921, gnomAD 0.01%). 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: 1347671). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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	RCV004009177	SCV004826481	uncertain significance	Malignant hyperthermia, susceptibility to, 1	2023-08-15	criteria provided, single submitter	clinical testing	This variant causes a C to G nucleotide substitution at the -5 position of intron 104 of the RYR1 gene. To our knowledge, functional 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 4/251496 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.