Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001226980 | SCV001399313 | uncertain significance | Epileptic encephalopathy | 2022-07-06 | criteria provided, single submitter | clinical testing | 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. ClinVar contains an entry for this variant (Variation ID: 954517). This variant has not been reported in the literature in individuals affected with RYR3-related conditions. This variant is present in population databases (rs191637587, gnomAD 0.01%). This sequence change replaces cysteine, which is neutral and slightly polar, with phenylalanine, which is neutral and non-polar, at codon 4146 of the RYR3 protein (p.Cys4146Phe). |
| Ambry Genetics | RCV002562618 | SCV003747994 | uncertain significance | Inborn genetic diseases | 2021-06-22 | criteria provided, single submitter | clinical testing | The c.12437G>T (p.C4146F) alteration is located in exon 89 (coding exon 89) of the RYR3 gene. This alteration results from a G to T substitution at nucleotide position 12437, causing the cysteine (C) at amino acid position 4146 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |