Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001054888 | SCV001219246 | uncertain significance | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2022-12-29 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 850669). This variant has not been reported in the literature in individuals affected with CASR-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 554 of the CASR protein (p.Ile554Phe). |
| Ambry Genetics | RCV002400312 | SCV002706527 | uncertain significance | Inborn genetic diseases; Nephrolithiasis/nephrocalcinosis | 2021-11-03 | criteria provided, single submitter | clinical testing | The p.I554F variant (also known as c.1660A>T), located in coding exon 5 of the CASR gene, results from an A to T substitution at nucleotide position 1660. The isoleucine at codon 554 is replaced by phenylalanine, an amino acid with highly similar 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. |