Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001373589 | SCV001570312 | uncertain significance | Epileptic encephalopathy | 2020-05-14 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, 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 (rs772157944, ExAC 0.008%). This sequence change replaces leucine with phenylalanine at codon 1461 of the RYR3 protein (p.Leu1461Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. |
| Ambry Genetics | RCV002548673 | SCV003710245 | uncertain significance | Inborn genetic diseases | 2022-07-14 | criteria provided, single submitter | clinical testing | The c.4381C>T (p.L1461F) alteration is located in exon 33 (coding exon 33) of the RYR3 gene. This alteration results from a C to T substitution at nucleotide position 4381, causing the leucine (L) at amino acid position 1461 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |