Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001063610 | SCV001228465 | uncertain significance | RYR1-Related Disorders | 2019-04-30 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with RYR1-related conditions. This sequence change replaces leucine with phenylalanine at codon 1045 of the RYR1 protein (p.Leu1045Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is not present in population databases (ExAC no frequency). 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"). 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. |