Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001304675 | SCV001493968 | uncertain significance | Epileptic encephalopathy | 2020-04-06 | criteria provided, single submitter | clinical testing | 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. 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: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with RYR3-related conditions. This variant is present in population databases (rs771548354, ExAC 0.009%). This sequence change replaces histidine with proline at codon 563 of the RYR3 protein (p.His563Pro). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and proline. |
Prevention |
RCV003405522 | SCV004106508 | uncertain significance | RYR3-related condition | 2023-03-13 | criteria provided, single submitter | clinical testing | The RYR3 c.1688A>C variant is predicted to result in the amino acid substitution p.His563Pro. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/15-33878217-A-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |