Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001220217 | SCV001392195 | uncertain significance | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2020-08-26 | 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 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 conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with alanine at codon 256 of the CASR protein (p.Val256Ala). The valine residue is highly conserved and there is a small physicochemical difference between valine and alanine. |
| Ambry Genetics | RCV002402661 | SCV002673161 | uncertain significance | Inborn genetic diseases; Nephrolithiasis/nephrocalcinosis | 2021-10-06 | criteria provided, single submitter | clinical testing | The p.V256A variant (also known as c.767T>C), located in coding exon 3 of the CASR gene, results from a T to C substitution at nucleotide position 767. The valine at codon 256 is replaced by alanine, an amino acid with 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. |
| Gene |
RCV003227936 | SCV003925047 | uncertain significance | not provided | 2022-11-11 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |