Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000056084 | SCV002237264 | pathogenic | Cholestanol storage disease | 2023-08-30 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Studies have shown that this variant is associated with altered splicing, resulting in an in-frame deletion in exon 8 or inclusion of intron 7 (PMID: 9392430). ClinVar contains an entry for this variant (Variation ID: 65844). This variant is also known as In 7 G-1>A. Disruption of this splice site has been observed in individual(s) with cerebrotendinous xanthomatosis (PMID: 9392430). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs587778785, gnomAD 0.003%). This sequence change affects an acceptor splice site in intron 7 of the CYP27A1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CYP27A1 are known to be pathogenic (PMID: 9392430, 10775536, 26937392). |
Gene |
RCV000056084 | SCV000087150 | pathologic | Cholestanol storage disease | 2013-08-01 | no assertion criteria provided | curation | Converted during submission to Pathogenic. |