ClinVar Miner

Submissions for variant NM_000784.4(CYP27A1):c.1175A>C (p.Glu392Ala)

gnomAD frequency: 0.00001  dbSNP: rs1245201394
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000595187 SCV000706427 uncertain significance not provided 2017-02-23 criteria provided, single submitter clinical testing
Counsyl RCV000665470 SCV000789600 uncertain significance Cholestanol storage disease 2017-02-07 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000665470 SCV002165306 uncertain significance Cholestanol storage disease 2024-10-21 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 392 of the CYP27A1 protein (p.Glu392Ala). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with cerebrotendinous xanthomatosis (PMID: 19373932). This variant is also known as E359A. ClinVar contains an entry for this variant (Variation ID: 500465). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt CYP27A1 protein function with a positive predictive value of 95%. This variant disrupts the p.Glu392 amino acid residue in CYP27A1. Other variant(s) that disrupt this residue have been observed in individuals with CYP27A1-related conditions (PMID: 27455001), which suggests that this may be a clinically significant amino acid residue. 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 RCV004701692 SCV005203556 uncertain significance not specified 2024-07-15 criteria provided, single submitter clinical testing Variant summary: CYP27A1 c.1175A>C (p.Glu392Ala) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251350 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1175A>C has been reported in the literature in at least one individual affected with Cerebrotendinous Xanthomatosis (e.g. Alcalay_2009). These data do not provide sufficient data to allow any conclusion about variant significance. To our knowledge, 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: 19373932). ClinVar contains an entry for this variant (Variation ID: 500465). Based on the evidence outlined above, the variant was classified as uncertain significance.

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