Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001908664 | SCV002158026 | uncertain significance | Cholestanol storage disease | 2022-06-25 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 513 of the CYP27A1 protein (p.Arg513Leu). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with clinical features of cerebrotendinous xanthomatosis (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Arg513 amino acid residue in CYP27A1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 28623566, 31743419, 32714376). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004690161 | SCV005185748 | uncertain significance | not specified | 2024-05-15 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV003892928 | SCV004710669 | uncertain significance | CYP27A1-related disorder | 2023-12-22 | no assertion criteria provided | clinical testing | The CYP27A1 c.1538G>T variant is predicted to result in the amino acid substitution p.Arg513Leu. To our knowledge, this variant has not been reported in the literature. Alternate nucleotide substitutions resulting in different missense changes at the same amino acid position (i.e. p.Arg513Cys and p.Arg513His) have been reported in individuals with cerebrotendinous xanthomatosis (see for example Chen et al. 2017. PubMed ID: 28623566; Ginanneschi et al. 2013. PubMed ID: 22878431). The c.1538G>T (p.Arg513Leu) variant is reported in 0.0009% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |