ClinVar Miner

Submissions for variant NM_000784.4(CYP27A1):c.1298G>A (p.Arg433Gln)

gnomAD frequency: 0.00002  dbSNP: rs201107032
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000272544 SCV000340628 uncertain significance not provided 2017-06-09 criteria provided, single submitter clinical testing
Invitae RCV001859658 SCV002308493 uncertain significance Cholestanol storage disease 2022-10-05 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 433 of the CYP27A1 protein (p.Arg433Gln). This variant is present in population databases (rs201107032, gnomAD 0.002%). This missense change has been observed in individual(s) with cerebrotendinous xanthomatosis (PMID: 33414089). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 287005). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CYP27A1 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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