Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002231381 | SCV000638068 | uncertain significance | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2023-06-20 | 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. 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 463946). This variant has not been reported in the literature in individuals affected with CASR-related conditions. This variant is present in population databases (rs763977493, gnomAD 0.003%). This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1012 of the CASR protein (p.Pro1012Thr). |
| Ambry Genetics | RCV002438357 | SCV002752824 | uncertain significance | Inborn genetic diseases; Nephrolithiasis/nephrocalcinosis | 2021-10-03 | criteria provided, single submitter | clinical testing | The p.P1012T variant (also known as c.3034C>A), located in coding exon 6 of the CASR gene, results from a C to A substitution at nucleotide position 3034. The proline at codon 1012 is replaced by threonine, 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. |