ClinVar Miner

Submissions for variant NM_000784.4(CYP27A1):c.475C>T (p.Gln159Ter) (rs72551314)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000444884 SCV000520934 likely pathogenic not provided 2018-11-28 criteria provided, single submitter clinical testing The Q159X variant has been reported previously in an individual with progressive spastic tetraparesis with no xanthomas, but with biochemical testing results indicative of cerebrotendinous xanthomatosis, who harbored another variant in the CYP27A1 gene; parental testing was not performed to confirm the variants were in trans (Verrips et al., 2000). This variant is predicted to cause loss of normal protein function through protein truncation or nonsense-mediated mRNA decay. The Q159X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret Q159X as a likely pathogenic variant.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000444884 SCV000860696 pathogenic not provided 2018-04-05 criteria provided, single submitter clinical testing
Invitae RCV000056118 SCV001220275 pathogenic Cholestanol storage disease 2020-07-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln159*) in the CYP27A1 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs72551314, ExAC 0.004%). This variant has been observed in an individual affected with cerebrotendinous xanthomatosis (PMID: 8931710). This variant is also known as Gln126* in the literature. ClinVar contains an entry for this variant (Variation ID: 65873). Loss-of-function variants in CYP27A1 are known to be pathogenic (PMID: 9392430, 10775536, 26937392). For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics, University of Leipzig Medical Center RCV000056118 SCV001440898 pathogenic Cholestanol storage disease 2019-01-01 criteria provided, single submitter clinical testing This variant was identified as compound heterozygous.
GeneReviews RCV000056118 SCV000087196 pathologic Cholestanol storage disease 2013-08-01 no assertion criteria provided curation Converted during submission to Pathogenic.

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