Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000702074 | SCV000830908 | uncertain significance | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2022-06-18 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with CASR-related conditions. This variant is present in population databases (rs755403770, gnomAD 0.0009%). This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 402 of the CASR protein (p.Ser402Arg). ClinVar contains an entry for this variant (Variation ID: 578925). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). |
| Gene |
RCV002253569 | SCV002525317 | uncertain significance | not provided | 2022-06-01 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Ambry Genetics | RCV002343541 | SCV002652022 | uncertain significance | Inborn genetic diseases; Nephrolithiasis/nephrocalcinosis | 2022-08-29 | criteria provided, single submitter | clinical testing | The p.S402R variant (also known as c.1206C>G), located in coding exon 3 of the CASR gene, results from a C to G substitution at nucleotide position 1206. The serine at codon 402 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |