Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics | RCV000711031 | SCV000841351 | uncertain significance | not provided | 2018-05-03 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001372372 | SCV001569016 | uncertain significance | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2020-07-25 | 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: "Benign"; Align-GVGD: "Class C65"). This variant disrupts the p.Arg66 amino acid residue in CASR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16740594, 25104082). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. This variant has not been reported in the literature in individuals with CASR-related conditions. ClinVar contains an entry for this variant (Variation ID: 585620). This sequence change replaces arginine with leucine at codon 66 of the CASR protein (p.Arg66Leu). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and leucine. This variant is not present in population databases (ExAC no frequency). |
| Ambry Genetics | RCV004026794 | SCV002723562 | uncertain significance | Nephrolithiasis/nephrocalcinosis | 2022-08-18 | criteria provided, single submitter | clinical testing | The p.R66L variant (also known as c.197G>T), located in coding exon 2 of the CASR gene, results from a G to T substitution at nucleotide position 197. The arginine at codon 66 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |