Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001059824 | SCV001224472 | uncertain significance | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2022-01-12 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with CASR-related conditions. 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: 854721). This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1055 of the CASR protein (p.Val1055Ile). |
| Ambry Genetics | RCV004031898 | SCV005035251 | uncertain significance | Nephrolithiasis/nephrocalcinosis | 2023-10-26 | criteria provided, single submitter | clinical testing | The p.V1055I variant (also known as c.3163G>A), located in coding exon 6 of the CASR gene, results from a G to A substitution at nucleotide position 3163. The valine at codon 1055 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. 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. |