ClinVar Miner

Submissions for variant NM_000784.4(CYP27A1):c.215T>A (p.Leu72Gln)

gnomAD frequency: 0.00014  dbSNP: rs138189735
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000633713 SCV000754985 uncertain significance Cholestanol storage disease 2022-10-21 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 72 of the CYP27A1 protein (p.Leu72Gln). This variant is present in population databases (rs138189735, gnomAD 0.03%). 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: 528492). 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. 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.
GeneDx RCV001579919 SCV002050638 uncertain significance not provided 2023-10-30 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Athena Diagnostics RCV001579919 SCV002770470 uncertain significance not provided 2021-10-14 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003420097 SCV004113365 uncertain significance CYP27A1-related disorder 2022-12-28 criteria provided, single submitter clinical testing The CYP27A1 c.215T>A variant is predicted to result in the amino acid substitution p.Leu72Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.026% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-219647120-T-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Natera, Inc. RCV000633713 SCV001462709 uncertain significance Cholestanol storage disease 2019-11-11 no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV001579919 SCV001809028 uncertain significance not provided no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV001579919 SCV001924208 uncertain significance not provided no assertion criteria provided clinical testing

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