Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000687843 | SCV000815432 | uncertain significance | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2022-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 4 of the CASR protein (p.Tyr4Cys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CASR-related conditions. ClinVar contains an entry for this variant (Variation ID: 567686). 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. 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. |
| Mendelics | RCV000987309 | SCV001136573 | uncertain significance | Familial hypocalciuric hypercalcemia 1 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004026278 | SCV005035210 | uncertain significance | Nephrolithiasis/nephrocalcinosis | 2023-10-28 | criteria provided, single submitter | clinical testing | The p.Y4C variant (also known as c.11A>G), located in coding exon 1 of the CASR gene, results from an A to G substitution at nucleotide position 11. The tyrosine at codon 4 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |