ClinVar Miner

Submissions for variant NM_000784.4(CYP27A1):c.1213C>T (p.Arg405Trp) (rs573951598)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000727395 SCV000708174 pathogenic not provided 2018-04-26 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000056078 SCV000915890 pathogenic Cholestanol storage disease 2018-10-16 criteria provided, single submitter clinical testing The CYP27A1 c.1213C>T (p.Arg405Trp) variant has been reported in at least six studies and is found in a total of 13 probands with cerebrotendinous xanthomatosis including two in a homozygous state and 11 in a compound heterozygous state (Verrips et al. 2000; Bartholdi et al. 2004; Pilo et al. 2011; Pilo-de-la-Fuente et al. 2011; Kauffman et al. 2012; Huijgen et al. 2012). Eight of the compound heterozygous probands are from two families (Verrips et al. 2000; Bartholdi et al. 2004). The p.Arg405Trp variant is absent from 150 controls and is reported at a frequency of 0.00003 in the total population of the Exome Aggregation Consortium. Based on the evidence, the p.Arg405Trp variant is classified as pathogenic for cerebrotendinous xanthomatosis. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000727395 SCV001447375 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Invitae RCV000056078 SCV001591691 pathogenic Cholestanol storage disease 2020-08-14 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 405 of the CYP27A1 protein (p.Arg405Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs573951598, ExAC 0.009%). This variant has been observed in individual(s) with cerebrotendinous xanthomatosis (PMID: 10775536, 21645175, 14999499). ClinVar contains an entry for this variant (Variation ID: 65838). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). This variant disrupts the p.Arg405 amino acid residue in CYP27A1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9186905, 28623566). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
GeneReviews RCV000056078 SCV000087143 pathologic Cholestanol storage disease 2013-08-01 no assertion criteria provided curation Converted during submission to 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.