Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001071002 | SCV001236283 | uncertain significance | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2019-11-18 | 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. 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. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CASR-related conditions. This variant is present in population databases (rs755997016, ExAC 0.002%). This sequence change replaces glycine with serine at codon 316 of the CASR protein (p.Gly316Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. |
| Ambry Genetics | RCV002375000 | SCV002686922 | uncertain significance | Inborn genetic diseases; Nephrolithiasis/nephrocalcinosis | 2022-04-19 | criteria provided, single submitter | clinical testing | The p.G316S variant (also known as c.946G>A), located in coding exon 3 of the CASR gene, results from a G to A substitution at nucleotide position 946. The glycine at codon 316 is replaced by serine, an amino acid with similar properties. This amino acid position is highly 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. |
| Fulgent Genetics, |
RCV002480440 | SCV002781263 | uncertain significance | Familial hypocalciuric hypercalcemia 1; Neonatal severe primary hyperparathyroidism; Epilepsy, idiopathic generalized, susceptibility to, 8; Autosomal dominant hypocalcemia 1 | 2022-05-17 | criteria provided, single submitter | clinical testing |