Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001210466 | SCV001381955 | uncertain significance | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2019-06-23 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with aspartic acid at codon 802 of the CASR protein (p.Asn802Asp). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and aspartic acid. 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. |
| Ambry Genetics | RCV002451456 | SCV002738551 | uncertain significance | Inborn genetic diseases; Nephrolithiasis/nephrocalcinosis | 2020-07-27 | criteria provided, single submitter | clinical testing | The p.N802D variant (also known as c.2404A>G), located in coding exon 6 of the CASR gene, results from an A to G substitution at nucleotide position 2404. The asparagine at codon 802 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. 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. |