Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001062657 | SCV001227472 | uncertain significance | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2019-04-09 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine with leucine at codon 734 of the CASR protein (p.Met734Leu). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and leucine. 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). |
| Ambry Genetics | RCV003160510 | SCV003855433 | uncertain significance | Inborn genetic diseases; Nephrolithiasis/nephrocalcinosis | 2022-11-20 | criteria provided, single submitter | clinical testing | The p.M734L variant (also known as c.2200A>T), located in coding exon 6 of the CASR gene, results from an A to T substitution at nucleotide position 2200. The methionine at codon 734 is replaced by leucine, 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. |