Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000535785 | SCV000638048 | uncertain significance | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2024-01-21 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 851 of the CASR protein (p.Cys851Ser). This variant is present in population databases (rs200777304, gnomAD 0.007%). This missense change has been observed in individual(s) with autosomal dominant hypoparathyroidism and/or familial benign hypocalciuric hypercalcaemia (PMID: 8733126, 10971459). ClinVar contains an entry for this variant (Variation ID: 463929). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change does not substantially affect CASR function (PMID: 20164288). 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 | RCV002431599 | SCV002740660 | uncertain significance | Inborn genetic diseases; Nephrolithiasis/nephrocalcinosis | 2021-07-16 | criteria provided, single submitter | clinical testing | The p.C851S variant (also known as c.2551T>A), located in coding exon 6 of the CASR gene, results from a T to A substitution at nucleotide position 2551. The cysteine at codon 851 is replaced by serine, an amino acid with dissimilar properties. This alteration was identified in 0/17 individuals diagnosed with familial hypocalciuric hypercalcemia and 1/198 controls (Guarnieri V et al. J Clin Endocrinol Metab, 2010 Apr;95:1819-29). This amino acid position is highly conserved in available vertebrate species. 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. |
Fulgent Genetics, |
RCV002476146 | SCV002784227 | uncertain significance | Familial hypocalciuric hypercalcemia 1; Neonatal severe primary hyperparathyroidism; Epilepsy, idiopathic generalized, susceptibility to, 8; Autosomal dominant hypocalcemia 1 | 2021-08-03 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003905381 | SCV004727844 | uncertain significance | CASR-related condition | 2023-11-08 | criteria provided, single submitter | clinical testing | The CASR c.2581T>A variant is predicted to result in the amino acid substitution p.Cys861Ser. This variant was reported in a family with presumed autosomal dominant hypoparathyroidism, but was detected in two unaffected family members and a different CASR variant was considered causative (Reported as T2551A, p.Cys851Ser in Baron. 1996. PubMed ID: 8733126). This variant is reported in 0.0077% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/3-122003352-T-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |