Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001071318 | SCV001236613 | uncertain significance | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2019-11-26 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). 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). This sequence change replaces glutamic acid with alanine at codon 499 of the CASR protein (p.Glu499Ala). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and alanine. |
| Ambry Genetics | RCV004030785 | SCV002701293 | uncertain significance | Nephrolithiasis/nephrocalcinosis | 2022-08-30 | criteria provided, single submitter | clinical testing | The p.E499A variant (also known as c.1496A>C), located in coding exon 4 of the CASR gene, results from an A to C substitution at nucleotide position 1496. The glutamic acid at codon 499 is replaced by alanine, an amino acid with dissimilar properties. This amino acid position is conserved. 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. |