Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001062165 | SCV001226945 | uncertain significance | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2023-05-20 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 423 of the CASR protein (p.Ala423Thr). This variant has not been reported in the literature in individuals affected with CASR-related conditions. 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 856658). |
| Ambry Genetics | RCV002374957 | SCV002685815 | uncertain significance | Inborn genetic diseases; Nephrolithiasis/nephrocalcinosis | 2022-05-21 | criteria provided, single submitter | clinical testing | The p.A423T variant (also known as c.1267G>A), located in coding exon 3 of the CASR gene, results from a G to A substitution at nucleotide position 1267. The alanine at codon 423 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |