Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002231729 | SCV000638008 | uncertain significance | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2022-06-08 | 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The asparagine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 385 of the CASR protein (p.Ser385Asn). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CASR-related conditions. ClinVar contains an entry for this variant (Variation ID: 463893). |
| Ambry Genetics | RCV002358497 | SCV002622691 | uncertain significance | Inborn genetic diseases; Nephrolithiasis/nephrocalcinosis | 2021-07-29 | criteria provided, single submitter | clinical testing | The p.S385N variant (also known as c.1154G>A), located in coding exon 3 of the CASR gene, results from a G to A substitution at nucleotide position 1154. The serine at codon 385 is replaced by asparagine, an amino acid with highly similar 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. |