ClinVar Miner

Submissions for variant NM_000784.4(CYP27A1):c.203T>G (p.Phe68Cys)

gnomAD frequency: 0.00001  dbSNP: rs587780327
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000116862 SCV000150936 uncertain significance not provided 2014-03-06 criteria provided, single submitter clinical testing
Counsyl RCV000664927 SCV000788964 uncertain significance Cholestanol storage disease 2016-12-23 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000664927 SCV003453929 uncertain significance Cholestanol storage disease 2022-10-25 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 68 of the CYP27A1 protein (p.Phe68Cys). This variant is present in population databases (rs587780327, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with CYP27A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 128883). 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) performed at Invitae indicates that this missense variant is not expected to disrupt CYP27A1 protein function. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003479010 SCV004223508 uncertain significance not specified 2023-11-08 criteria provided, single submitter clinical testing Variant summary: CYP27A1 c.203T>G (p.Phe68Cys) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251328 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, c.203T>G has not been reported in the literature in individuals affected with Cerebrotendinous Xanthomatosis and no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 34103343). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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