Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001066657 | SCV001231672 | uncertain significance | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2021-10-08 | 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 alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with CASR-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with alanine at codon 1006 of the CASR protein (p.Thr1006Ala). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and alanine. |
| Ambry Genetics | RCV002436663 | SCV002753319 | uncertain significance | Inborn genetic diseases; Nephrolithiasis/nephrocalcinosis | 2022-08-23 | criteria provided, single submitter | clinical testing | The p.T1006A variant (also known as c.3016A>G), located in coding exon 6 of the CASR gene, results from an A to G substitution at nucleotide position 3016. The threonine at codon 1006 is replaced by alanine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. 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. |