ClinVar Miner

Submissions for variant NM_000784.4(CYP27A1):c.562C>T (p.Arg188Ter)

gnomAD frequency: 0.00004  dbSNP: rs188850202
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000987032 SCV001136214 pathogenic Cholestanol storage disease 2019-05-28 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000987032 SCV001207851 pathogenic Cholestanol storage disease 2024-01-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg188*) in the CYP27A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CYP27A1 are known to be pathogenic (PMID: 9392430, 10775536, 26937392). This variant is present in population databases (rs188850202, gnomAD 0.03%). This premature translational stop signal has been observed in individual(s) with cerebrotendinous xanthomatosis (PMID: 28623566). 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: 801897). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000987032 SCV004192660 pathogenic Cholestanol storage disease 2024-01-16 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003928633 SCV004742287 pathogenic CYP27A1-related disorder 2023-10-24 criteria provided, single submitter clinical testing The CYP27A1 c.562C>T variant is predicted to result in premature protein termination (p.Arg188*). This variant has been reported in the compound heterozygous state in an individual presenting with Cerebrotendinous xanthomatosis (CTX) (Family 4, Table 1, Chen et al. 2017. PubMed ID: 28623566). This variant is reported in 0.035% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-219677060-C-T). Nonsense variants in CYP27A1 are expected to be pathogenic. This variant is interpreted as pathogenic.
Natera, Inc. RCV000987032 SCV002078774 pathogenic Cholestanol storage disease 2020-10-27 no assertion criteria provided clinical testing

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