Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002232985 | SCV000834788 | uncertain significance | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2018-04-09 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine with histidine at codon 744 of the CASR protein (p.Tyr744His). The tyrosine residue is highly conserved and there is a moderate physicochemical difference between tyrosine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CASR-related disease. 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |
| Ambry Genetics | RCV002422603 | SCV002725395 | uncertain significance | Inborn genetic diseases; Nephrolithiasis/nephrocalcinosis | 2022-04-20 | criteria provided, single submitter | clinical testing | The p.Y744H variant (also known as c.2230T>C), located in coding exon 6 of the CASR gene, results from a T to C substitution at nucleotide position 2230. The tyrosine at codon 744 is replaced by histidine, an amino acid with 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. |