Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000823382 | SCV000964239 | pathogenic | RYR1-related disorder | 2018-11-25 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This missense change is located in a region of the RYR1 protein where a significant number of previously reported RYR1 missense mutations are found (PMID: 16084090). These observations suggest that a previously unreported missense substitution within this region may affect protein function, but experiments have not been done to test this possibility. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has been observed to be de novo in an individual affected with myopathy (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with glutamic acid at codon 4896 of the RYR1 protein (p.Gly4896Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. |
Revvity Omics, |
RCV003130077 | SCV003812478 | uncertain significance | not provided | 2022-05-30 | criteria provided, single submitter | clinical testing |