ClinVar Miner

Submissions for variant NM_000784.4(CYP27A1):c.1420C>T (p.Arg474Trp) (rs121908098)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000004481 SCV000792409 likely pathogenic Cholestanol storage disease 2017-06-22 criteria provided, single submitter clinical testing
Invitae RCV000004481 SCV000960673 pathogenic Cholestanol storage disease 2019-12-03 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 474 of the CYP27A1 protein (p.Arg474Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs121908098, ExAC 0.01%). This variant has been observed to be homozygous or in combination with another CYP27A1 variant in individuals affected with cerebrotendinous xanthomatosis (PMID: 7915755, 10406988, 12270007, 17319284, 22336472, 29321515), and has been shown to be on the opposite chromosome (in trans) from a pathogenic variant in an affected individual (PMID: 11903362). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. This variant is also known as p.Arg441Trp in the literature. ClinVar contains an entry for this variant (Variation ID: 4259). Experimental studies have shown that this missense change impairs enzyme activity (PMID: 12270007). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000004481 SCV000024654 pathogenic Cholestanol storage disease 1994-06-01 no assertion criteria provided literature only
GeneReviews RCV000004481 SCV000087159 pathologic Cholestanol storage disease 2013-08-01 no assertion criteria provided curation Converted during submission to Pathogenic.
Department of Rehabilitation Medicine, Incheon St. Mary’s Hospital,College of Medicine, The Catholic University of Korea RCV000004481 SCV000882743 pathogenic Cholestanol storage disease 2019-02-11 no assertion criteria provided research

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