Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ce |
RCV001531954 | SCV001747304 | pathogenic | not provided | 2021-08-01 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV003470853 | SCV004190833 | pathogenic | Cholestanol storage disease | 2023-02-01 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV003470853 | SCV004293975 | pathogenic | Cholestanol storage disease | 2024-02-14 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 8 of the CYP27A1 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with clinical features of CYP27A1-related conditions (PMID: 27084087). ClinVar contains an entry for this variant (Variation ID: 1176421). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts a region of the CYP27A1 protein in which other variant(s) (p.Arg513Cys) have been determined to be pathogenic (PMID: 28623566, 31743419, 32714376, 34012265). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
Fulgent Genetics, |
RCV003470853 | SCV005647760 | likely pathogenic | Cholestanol storage disease | 2024-01-20 | criteria provided, single submitter | clinical testing |