ClinVar Miner

Submissions for variant NM_000784.4(CYP27A1):c.776A>G (p.Lys259Arg) (rs72551317)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000056144 SCV000797944 likely pathogenic Cholestanol storage disease 2018-02-15 criteria provided, single submitter clinical testing
Invitae RCV000056144 SCV001382860 likely pathogenic Cholestanol storage disease 2020-08-24 criteria provided, single submitter clinical testing This sequence change replaces lysine with arginine at codon 259 of the CYP27A1 protein (p.Lys259Arg). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and arginine. This variant is present in population databases (rs72551317, ExAC 0.003%). This variant has been observed in several individuals affected with cerebrotendinous xanthomatosis (PMID: 10775536, 22878431). ClinVar contains an entry for this variant (Variation ID: 65898). This variant is also known as p.Lys226Arg in the literature. This variant has been reported not to substantially affect CYP27A1 protein function (PMID: 17697869). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
GeneReviews RCV000056144 SCV000087225 pathologic Cholestanol storage disease 2013-08-01 no assertion criteria provided curation Converted during submission to Pathogenic.

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