Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002469991 | SCV002766097 | likely pathogenic | Cholestanol storage disease | 2022-11-15 | criteria provided, single submitter | clinical testing | Variant summary: CYP27A1 c.1126delC (p.Gln376SerfsX32) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been reported in association with Cerebrotendinous xanthomatosis in HGMD.The variant allele was found at a frequency of 4e-06 in 251404 control chromosomes. To our knowledge, no occurrence of c.1126delC in individuals affected with Cerebrotendinous Xanthomatosis (CTX), however, an infant diagnosed with CTX with the same expected protein variant (p.E408*) has been reported in the literature (von Bahr_2005). No experimental evidence demonstrating the impact of this variant on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Labcorp Genetics |
RCV002469991 | SCV003459074 | pathogenic | Cholestanol storage disease | 2023-08-02 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 1804694). 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 0.007%). This sequence change creates a premature translational stop signal (p.Gln376Serfs*32) in the CYP27A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CYP27A1 are known to be pathogenic (PMID: 9392430, 10775536, 26937392). |
| Baylor Genetics | RCV002469991 | SCV005059330 | likely pathogenic | Cholestanol storage disease | 2024-01-21 | criteria provided, single submitter | clinical testing |