Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001052412 | SCV001216622 | uncertain significance | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2021-03-15 | criteria provided, single submitter | clinical testing | 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 present in population databases (rs377233360, ExAC 0.01%). This sequence change replaces glycine with glutamic acid at codon 518 of the CASR protein (p.Gly518Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. |
| Ambry Genetics | RCV004031642 | SCV002704881 | uncertain significance | Nephrolithiasis/nephrocalcinosis | 2023-12-10 | criteria provided, single submitter | clinical testing | The p.G518E variant (also known as c.1553G>A), located in coding exon 4 of the CASR gene, results from a G to A substitution at nucleotide position 1553. The glycine at codon 518 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |