Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001047702 | SCV001211681 | uncertain significance | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2020-10-10 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with tyrosine at codon 398 of the CASR protein (p.Asp398Tyr). The aspartic acid residue is highly conserved and there is a large physicochemical difference between aspartic acid and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CASR-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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. |
| Genomic Medicine Center of Excellence, |
RCV003989125 | SCV004805814 | uncertain significance | Familial hypocalciuric hypercalcemia 1 | 2024-03-29 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004031480 | SCV005034759 | uncertain significance | Nephrolithiasis/nephrocalcinosis | 2023-07-06 | criteria provided, single submitter | clinical testing | The p.D398Y variant (also known as c.1192G>T), located in coding exon 3 of the CASR gene, results from a G to T substitution at nucleotide position 1192. The aspartic acid at codon 398 is replaced by tyrosine, 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. |