Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000801525 | SCV000941302 | uncertain significance | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2022-08-20 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 460 of the CASR protein (p.Val460Ile). 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. ClinVar contains an entry for this variant (Variation ID: 647098). This variant has not been reported in the literature in individuals affected with CASR-related conditions. This variant is present in population databases (rs753189535, gnomAD 0.008%). |
| Ambry Genetics | RCV002386427 | SCV002698173 | uncertain significance | Inborn genetic diseases; Nephrolithiasis/nephrocalcinosis | 2021-09-07 | criteria provided, single submitter | clinical testing | The p.V460I variant (also known as c.1378G>A) is located in coding exon 4 of the CASR gene. The valine at codon 460 is replaced by isoleucine, an amino acid with highly similar properties. This change occurs in the first base pair of coding exon 4. 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. |