Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000544351 | SCV000638006 | uncertain significance | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2023-11-12 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 382 of the CASR protein (p.Asp382Asn). This variant is present in population databases (rs199980578, gnomAD 0.01%). 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: 463892). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The asparagine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 | RCV002330870 | SCV001178530 | uncertain significance | Inborn genetic diseases; Nephrolithiasis/nephrocalcinosis | 2022-11-23 | criteria provided, single submitter | clinical testing | The p.D382N variant (also known as c.1144G>A), located in coding exon 3 of the CASR gene, results from a G to A substitution at nucleotide position 1144. The aspartic acid at codon 382 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species, and asparagine is the reference amino acid in other vertebrate species. 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. |
Institute for Clinical Genetics, |
RCV003144333 | SCV002010664 | uncertain significance | not provided | 2021-11-03 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002491010 | SCV002798227 | uncertain significance | Familial hypocalciuric hypercalcemia 1; Neonatal severe primary hyperparathyroidism; Epilepsy, idiopathic generalized, susceptibility to, 8; Autosomal dominant hypocalcemia 1 | 2022-01-04 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV003144333 | SCV003829246 | uncertain significance | not provided | 2021-05-14 | criteria provided, single submitter | clinical testing | |
Gene |
RCV003144333 | SCV003925941 | uncertain significance | not provided | 2023-05-16 | criteria provided, single submitter | clinical testing | Identified heterozygous in a patient with familial hypocalciuric hypercalcemia (Shaw-Jone et al., 2022); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 35789394) |