Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Centre for Mendelian Genomics, |
RCV001198250 | SCV001369124 | uncertain significance | Hypercalcemia, infantile, 1 | 2016-01-01 | criteria provided, single submitter | clinical testing | This variant was classified as: Uncertain significance. This variant was inherited from a parent. |
| Labcorp Genetics |
RCV001350278 | SCV001544667 | uncertain significance | not provided | 2022-04-22 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 439 of the CYP24A1 protein (p.Arg439Cys). This variant is present in population databases (rs374292194, gnomAD 0.008%). This missense change has been observed in individual(s) with hypercalcemia (PMID: 26214117, 32375123). ClinVar contains an entry for this variant (Variation ID: 931571). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CYP24A1 protein function. Experimental studies have shown that this missense change affects CYP24A1 function (PMID: 26214117). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
| Center For Human Genetics And Laboratory Diagnostics, |
RCV001198250 | SCV004014831 | pathogenic | Hypercalcemia, infantile, 1 | 2023-06-26 | criteria provided, single submitter | clinical testing |