Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001244531 | SCV001417757 | uncertain significance | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2021-04-21 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with cysteine at codon 873 of the CASR protein (p.Arg873Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CASR-related conditions. This variant is not present in population databases (ExAC no frequency). |
| Gene |
RCV001545975 | SCV001765407 | uncertain significance | not provided | 2019-11-14 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Ambry Genetics | RCV004034788 | SCV002744575 | uncertain significance | Nephrolithiasis/nephrocalcinosis | 2022-05-18 | criteria provided, single submitter | clinical testing | The p.R873C variant (also known as c.2617C>T), located in coding exon 6 of the CASR gene, results from a C to T substitution at nucleotide position 2617. The arginine at codon 873 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. 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. |