Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000523819 | SCV000616735 | likely pathogenic | not provided | 2022-05-19 | criteria provided, single submitter | clinical testing | Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge |
| Invitae | RCV001050632 | SCV001214751 | likely pathogenic | Glycogen storage disease due to muscle and heart glycogen synthase deficiency | 2022-03-29 | criteria provided, single submitter | clinical testing | This variant results in the deletion of part of exon 2 (c.119-2_120del) of the GYS1 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 GYS1 are known to be pathogenic (PMID: 17928598, 19699667). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 449031). This variant has not been reported in the literature in individuals affected with GYS1-related conditions. This variant is not present in population databases (gnomAD no frequency). |