Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001051054 | SCV001215187 | uncertain significance | Epileptic encephalopathy | 2019-03-11 | 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with RYR3-related conditions. This variant is present in population databases (rs368930817, ExAC 0.003%). This sequence change replaces isoleucine with valine at codon 2047 of the RYR3 protein (p.Ile2047Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. |
| Ambry Genetics | RCV003160399 | SCV003907419 | uncertain significance | Inborn genetic diseases | 2023-02-22 | criteria provided, single submitter | clinical testing | The c.6139A>G (p.I2047V) alteration is located in exon 40 (coding exon 40) of the RYR3 gene. This alteration results from a A to G substitution at nucleotide position 6139, causing the isoleucine (I) at amino acid position 2047 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |