Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ce |
RCV001092428 | SCV001248935 | pathogenic | not provided | 2018-01-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000056113 | SCV003524916 | pathogenic | Cholestanol storage disease | 2023-10-06 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 145 of the CYP27A1 protein (p.Gly145Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with cerebrotendinous xanthomatosis (PMID: 20402754; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 65868). 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 CYP27A1 protein function. This variant disrupts the Gly145 amino acid residue in CYP27A1. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV000056113 | SCV000087190 | pathologic | Cholestanol storage disease | 2013-08-01 | no assertion criteria provided | curation | Converted during submission to Pathogenic. |