ClinVar Miner

Submissions for variant NM_000784.4(CYP27A1):c.67dup (p.His23fs) (rs1559384522)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001008477 SCV001168248 likely pathogenic not provided 2018-12-07 criteria provided, single submitter clinical testing The c.67dupC variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.67dupC variant causes a frameshift starting with codon Histidine 23, changes this amino acid to a Proline residue and creates a premature Stop codon at position 158 of the new reading frame, denoted p.His23ProfsX158. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Furthermore, the c.67dupC variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Invitae RCV001203126 SCV001374273 pathogenic Cholestanol storage disease 2020-08-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.His23Profs*158) in the CYP27A1 gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has not been reported in the literature in individuals with CYP27A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 817356). Loss-of-function variants in CYP27A1 are known to be pathogenic (PMID: 9392430, 10775536, 26937392). For these reasons, this variant has been classified as Pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.