Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001051183 | SCV001215325 | uncertain significance | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2022-11-07 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 359 of the CASR protein (p.His359Arg). This variant is not present in population databases (gnomAD no frequency). 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 C0"). ClinVar contains an entry for this variant (Variation ID: 847599). This variant has not been reported in the literature in individuals affected with CASR-related conditions. |
| Ambry Genetics | RCV002416386 | SCV002719726 | uncertain significance | Inborn genetic diseases; Nephrolithiasis/nephrocalcinosis | 2022-09-12 | criteria provided, single submitter | clinical testing | The p.H359R variant (also known as c.1076A>G), located in coding exon 3 of the CASR gene, results from an A to G substitution at nucleotide position 1076. The histidine at codon 359 is replaced by arginine, 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. |