Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001985459 | SCV002222239 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but 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 conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with histidine at codon 957 of the CASR protein (p.Gln957His). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and histidine. |
| Ambry Genetics | RCV004043759 | SCV003858280 | uncertain significance | Nephrolithiasis/nephrocalcinosis | 2022-12-13 | criteria provided, single submitter | clinical testing | The p.Q957H variant (also known as c.2871G>C), located in coding exon 6 of the CASR gene, results from a G to C substitution at nucleotide position 2871. The glutamine at codon 957 is replaced by histidine, 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. |