Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003556068 | SCV004298099 | pathogenic | not provided | 2023-04-07 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 322 of the CYP24A1 protein (p.Glu322Lys). This variant is present in population databases (rs387907324, gnomAD 0.007%). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects CYP24A1 function (PMID: 21675912). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CYP24A1 protein function. ClinVar contains an entry for this variant (Variation ID: 29681). This missense change has been observed in individual(s) with clinical features of CYP24A1-related conditions (PMID: 21675912, 28470390, 33099630, 34307984, 34662328). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. |
OMIM | RCV000033211 | SCV000057058 | pathogenic | Hypercalcemia, infantile, 1 | 2011-11-03 | no assertion criteria provided | literature only |