Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002923849 | SCV003274690 | uncertain significance | RYR1-related disorder | 2024-01-01 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 4188 of the RYR1 protein (p.Arg4188His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 2063479). 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 expected to disrupt RYR1 protein function with a positive predictive value of 95%. 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. |
| Ambry Genetics | RCV004673748 | SCV005161780 | uncertain significance | Inborn genetic diseases | 2024-05-24 | criteria provided, single submitter | clinical testing | The c.12563G>A (p.R4188H) alteration is located in exon 90 (coding exon 90) of the RYR1 gene. This alteration results from a G to A substitution at nucleotide position 12563, causing the arginine (R) at amino acid position 4188 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |