Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Greenwood Genetic Center Diagnostic Laboratories, |
RCV001806882 | SCV002051508 | likely pathogenic | not provided | 2020-12-08 | criteria provided, single submitter | clinical testing | PP2, PP3, PM1, PM2 |
| Ambry Genetics | RCV004040907 | SCV005035258 | uncertain significance | Nephrolithiasis/nephrocalcinosis | 2023-11-06 | criteria provided, single submitter | clinical testing | The p.G222R variant (also known as c.664G>A), located in coding exon 3 of the CASR gene, results from a G to A substitution at nucleotide position 664. The glycine at codon 222 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Victorian Clinical Genetics Services, |
RCV004785317 | SCV005400359 | uncertain significance | Familial hypocalciuric hypercalcemia 1 | 2024-09-21 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3A. Following criteria are met: 0103 - Dominant negative and loss of function are known mechanisms of disease in this gene and are associated with hypocalciuric hypercalcaemia (MIM#145980) and neonatal hyperparathyroidism (MIM#239200). Gain of function is associated with hypocalcaemia, with or without Bartter syndrome (MIM#601198) (PMIDs: 22422767, 26646938). (I) 0108 - This gene is associated with both recessive and dominant disease. (OMIM). (I) 0115 - Variants in this gene are known to have variable expressivity. Intrafamilial variability has been reported (PMID: 11807402). (I) 0200 - Variant is predicted to result in a missense amino acid change from glycine to arginine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0600 - Variant is located in the annotated ligand binding domain (DECIPHER, NCBI). (I) 0710 - Another missense variant comparable to the one identified in this case has inconclusive previous evidence for pathogenicity. An alternative change, p.(Gly222Glu), has been described as VUS in ClinVar, and without classification in an individual with hypocalciuric hypercalcaemia (PMID: 30407919). (I) 0803 - This variant has limited previous evidence of pathogenicity in an unrelated individual. This variant has previously been reported as likely pathogenic (ClinVar). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |