Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000487366 | SCV000572591 | likely pathogenic | not provided | 2018-01-11 | criteria provided, single submitter | clinical testing | The c.3964_3982dup19 variant causes a frameshift starting with codon Asparagine 1328, changes this amino acid to a Glycine residue and creates a premature Stop codon at position 9 of the new reading frame, denoted p.Asp1328GlyfsX9. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.3964_3982dup19 variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Although this variant has not been reported previously to our knowledge, other loss-of-function variants in the RYR1 gene have been reported in the Human Gene Mutation Database in association with RYR1-related disorders (Stenson et al., 2014). |
Labcorp Genetics |
RCV001380724 | SCV001578876 | pathogenic | RYR1-related disorder | 2023-11-25 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asp1328Glyfs*9) in the RYR1 gene. It is expected to result in an absent or disrupted protein product. 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: 422979). For these reasons, this variant has been classified as Pathogenic. |
Revvity Omics, |
RCV000487366 | SCV002019110 | likely pathogenic | not provided | 2019-02-20 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002481528 | SCV002791329 | 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 | 2021-12-05 | criteria provided, single submitter | clinical testing |