Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001368805 | SCV001565218 | uncertain significance | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2023-06-09 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 1059510). This variant has not been reported in the literature in individuals affected with CASR-related conditions. This variant is present in population databases (rs778165189, gnomAD 0.0009%). This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 464 of the CASR protein (p.Leu464Val). |
| Fulgent Genetics, |
RCV002476682 | SCV002778629 | uncertain significance | Familial hypocalciuric hypercalcemia 1; Neonatal severe primary hyperparathyroidism; Epilepsy, idiopathic generalized, susceptibility to, 8; Autosomal dominant hypocalcemia 1 | 2022-02-25 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004037059 | SCV005034762 | uncertain significance | Nephrolithiasis/nephrocalcinosis | 2023-04-19 | criteria provided, single submitter | clinical testing | The p.L464V variant (also known as c.1390C>G), located in coding exon 4 of the CASR gene, results from a C to G substitution at nucleotide position 1390. The leucine at codon 464 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. 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. |