Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000461913 | SCV000550991 | uncertain significance | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2021-07-14 | 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 C25"). This sequence change replaces serine with leucine at codon 132 of the CASR protein (p.Ser132Leu). The serine residue is highly conserved and there is a large physicochemical difference between serine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CASR-related disease. ClinVar contains an entry for this variant (Variation ID: 410352). |
| Ambry Genetics | RCV003168825 | SCV003855421 | uncertain significance | Inborn genetic diseases; Nephrolithiasis/nephrocalcinosis | 2022-11-05 | criteria provided, single submitter | clinical testing | The p.S132L variant (also known as c.395C>T), located in coding exon 2 of the CASR gene, results from a C to T substitution at nucleotide position 395. The serine at codon 132 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is conserved. 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. |