ClinVar Miner

Submissions for variant NM_000784.4(CYP27A1):c.1435C>T (p.Arg479Cys) (rs72551322)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000004476 SCV000754984 pathogenic Cholestanol storage disease 2019-12-31 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 479 of the CYP27A1 protein (p.Arg479Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs72551322, ExAC 0.01%). This variant has been reported in as homozygous or in combination with another CYP27A1 variant in individuals and families affected with cerebrotendinous xanthomatosis (PMID: 2019602, 21073839, 24584636). This variant is also known as p.Arg446Cys in the literature. ClinVar contains an entry for this variant (Variation ID: 4254). Experimental studies have shown that this missense change impairs enzyme function in vitro (PMID: 2019602). This variant disrupts the p.Arg479 amino acid residue in CYP27A1. Other variants that disrupt this residue have been observed in individuals with CYP27A1-related conditions (PMID: 16278884, 29095540), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000733099 SCV000861118 pathogenic not provided 2018-05-03 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000004476 SCV001298664 uncertain significance Cholestanol storage disease 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
OMIM RCV000004476 SCV000024649 pathogenic Cholestanol storage disease 1991-04-25 no assertion criteria provided literature only
GeneReviews RCV000004476 SCV000087163 pathologic Cholestanol storage disease 2013-08-01 no assertion criteria provided curation Converted during submission to Pathogenic.

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