Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002233475 | SCV000761041 | uncertain significance | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2020-12-17 | 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 lysine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CASR-related disease. This variant is present in population databases (rs760190284, ExAC 0.03%). This sequence change replaces arginine with lysine at codon 375 of the CASR protein (p.Arg375Lys). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and lysine. |
Ambry Genetics | RCV002440265 | SCV002750781 | uncertain significance | Inborn genetic diseases; Nephrolithiasis/nephrocalcinosis | 2021-12-20 | criteria provided, single submitter | clinical testing | The p.R375K variant (also known as c.1124G>A), located in coding exon 3 of the CASR gene, results from a G to A substitution at nucleotide position 1124. The arginine at codon 375 is replaced by lysine, 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. |