Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001231828 | SCV001404361 | uncertain significance | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2023-03-09 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant  is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 958630). This variant has not been reported in the literature in individuals affected with CASR-related conditions. This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 894 of the CASR protein (p.Val894Leu). |
| Ambry Genetics | RCV002436907 | SCV002744805 | uncertain significance | Inborn genetic diseases; Nephrolithiasis/nephrocalcinosis | 2022-11-19 | criteria provided, single submitter | clinical testing | The p.V894L variant (also known as c.2680G>C), located in coding exon 6 of the CASR gene, results from a G to C substitution at nucleotide position 2680. The valine at codon 894 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is not well 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. |