ClinVar Miner

Submissions for variant NM_000784.4(CYP27A1):c.1184G>A (p.Arg395His) (rs587778778)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000593893 SCV000709264 likely pathogenic not provided 2017-06-13 criteria provided, single submitter clinical testing
Counsyl RCV000056074 SCV000800610 uncertain significance Cholestanol storage disease 2017-10-25 criteria provided, single submitter clinical testing
Invitae RCV000056074 SCV001229624 likely pathogenic Cholestanol storage disease 2019-12-13 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 395 of the CYP27A1 protein (p.Arg395His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant also falls at the last nucleotide of exon 6 of the CYP27A1 coding sequence, which is part of the consensus splice site for this exon. This variant is present in population databases (rs587778778, ExAC 0.003%). This variant has been observed in individual(s) with cerebrotendinous xanthomatosis (PMID: 8950197). This variant is also known as Arg362His in the literature. ClinVar contains an entry for this variant (Variation ID: 65834). 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"). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 9548584, 17697869). 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.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000593893 SCV001248937 pathogenic not provided 2018-01-01 criteria provided, single submitter clinical testing
GeneReviews RCV000056074 SCV000087139 pathologic Cholestanol storage disease 2013-08-01 no assertion criteria provided curation Converted during submission to Pathogenic.

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