Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000655504 | SCV000777435 | uncertain significance | RYR1-related disorder | 2022-07-06 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 3685 of the RYR1 protein (p.Glu3685Gln). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RYR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 544382). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RYR1 protein function. 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. |
| Revvity Omics, |
RCV003133477 | SCV003812565 | uncertain significance | not provided | 2021-03-19 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004025981 | SCV004945796 | uncertain significance | Inborn genetic diseases | 2024-01-04 | criteria provided, single submitter | clinical testing | The c.11053G>C (p.E3685Q) alteration is located in exon 76 (coding exon 76) of the RYR1 gene. This alteration results from a G to C substitution at nucleotide position 11053, causing the glutamic acid (E) at amino acid position 3685 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |