Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000704054 | SCV000832987 | uncertain significance | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2020-10-08 | 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 disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with glutamine at codon 312 of the CASR protein (p.His312Gln). The histidine residue is moderately conserved and there is a small physicochemical difference between histidine and glutamine. |
| Ambry Genetics | RCV002442528 | SCV002682347 | uncertain significance | Inborn genetic diseases; Nephrolithiasis/nephrocalcinosis | 2021-11-01 | criteria provided, single submitter | clinical testing | The p.H312Q variant (also known as c.936C>G), located in coding exon 3 of the CASR gene, results from a C to G substitution at nucleotide position 936. The histidine at codon 312 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |