Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002387141 | SCV002695429 | uncertain significance | Cardiovascular phenotype | 2022-04-03 | criteria provided, single submitter | clinical testing | The p.M326V variant (also known as c.976A>G), located in coding exon 5 of the CYP27A1 gene, results from an A to G substitution at nucleotide position 976. The methionine at codon 326 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003094869 | SCV003510788 | uncertain significance | Cholestanol storage disease | 2022-09-27 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 326 of the CYP27A1 protein (p.Met326Val). 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. 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 not expected to disrupt CYP27A1 protein function. This variant has not been reported in the literature in individuals affected with CYP27A1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). |