Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678325 | SCV000804386 | likely pathogenic | Central core myopathy; Malignant hyperthermia, susceptibility to, 1 | 2017-10-04 | criteria provided, single submitter | provider interpretation | This variant was identified in a 3 year old male with autism spectrum disorder, global developmental delay, hypotonia, and plagiocephaly. It was inherited from a healthy mother with no relevant history of developmental or neuromuscular disorder. This variant is absent from the gnomAD database and is expected to affect splicing since it alters a canonical splice site. This variant has not been reported previously in the literature, to our knowledge. A second variant of uncertain significance was identified in trans, but clinical correlation with recessive RYR1-related disorders was thought to be poor. |
| Fulgent Genetics, |
RCV002493120 | SCV002790377 | likely pathogenic | Central core myopathy; Malignant hyperthermia, susceptibility to, 1; Congenital multicore myopathy with external ophthalmoplegia; Congenital myopathy with fiber type disproportion; King Denborough syndrome | 2021-11-16 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV003591771 | SCV004368878 | likely pathogenic | RYR1-related disorder | 2023-08-24 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 48 of the RYR1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in RYR1 are known to be pathogenic (PMID: 23919265, 25960145, 28818389, 30611313). This variant is not present in population databases (gnomAD no frequency). 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: 560259). 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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |