Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000468483 | SCV000551003 | uncertain significance | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2023-11-10 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 896 of the CASR protein (p.Arg896His). This variant is present in population databases (no rsID available, gnomAD 0.007%). This missense change has been observed in individual(s) with pancreatitis (PMID: 16497624). ClinVar contains an entry for this variant (Variation ID: 410364). 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 affects CASR function (PMID: 20798521). 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 | RCV002319003 | SCV001177238 | uncertain significance | Inborn genetic diseases; Nephrolithiasis/nephrocalcinosis | 2019-06-04 | criteria provided, single submitter | clinical testing | The p.R896H variant (also known as c.2687G>A), located in coding exon 6 of the CASR gene, results from a G to A substitution at nucleotide position 2687. The arginine at codon 896 is replaced by histidine, an amino acid with highly similar properties. This variant has been detected in a proband with chronic pancreatitis (CP) who also had SPINK1 p.N34S. Relatives with only CASR p.R896H were not reported to have CP (Felderbauer P et al. Scand. J. Gastroenterol., 2006 Mar;41:343-8). One experimental study suggested this variant may alter protein function (Stepanchick A et al. Cell. Physiol. Biochem., 2010 Aug;26:363-74). 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, |
RCV002480419 | SCV002801312 | uncertain significance | Familial hypocalciuric hypercalcemia 1; Neonatal severe primary hyperparathyroidism; Epilepsy, idiopathic generalized, susceptibility to, 8; Autosomal dominant hypocalcemia 1 | 2022-02-25 | criteria provided, single submitter | clinical testing |