Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001243613 | SCV001416781 | uncertain significance | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2019-10-31 | 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 disruptive, 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 aspartic acid with valine at codon 50 of the CASR protein (p.Asp50Val). The aspartic acid residue is highly conserved and there is a large physicochemical difference between aspartic acid and valine. |
Ambry Genetics | RCV002393636 | SCV002702286 | uncertain significance | Inborn genetic diseases; Nephrolithiasis/nephrocalcinosis | 2022-02-07 | criteria provided, single submitter | clinical testing | The p.D50V variant (also known as c.149A>T), located in coding exon 1 of the CASR gene, results from an A to T substitution at nucleotide position 149. The aspartic acid at codon 50 is replaced by valine, an amino acid with highly dissimilar properties. This amino acid position is conserved. 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. |