Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000797766 | SCV000937345 | uncertain significance | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2021-10-17 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with arginine at codon 609 of the CASR protein (p.Thr609Arg). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and arginine. This variant is not present in population databases (ExAC 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 C15"). This variant has not been reported in the literature in individuals affected with CASR-related conditions. |
| Ambry Genetics | RCV003166161 | SCV003858295 | uncertain significance | Inborn genetic diseases; Nephrolithiasis/nephrocalcinosis | 2023-03-14 | criteria provided, single submitter | clinical testing | The p.T609R variant (also known as c.1826C>G), located in coding exon 6 of the CASR gene, results from a C to G substitution at nucleotide position 1826. The threonine at codon 609 is replaced by arginine, an amino acid with similar 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. |