Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001009202 | SCV001169021 | likely pathogenic | not provided | 2019-01-14 | criteria provided, single submitter | clinical testing | The c.1005delT variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.1005delT variant causes a frameshift starting with codon Glycine 336, changes this amino acid to a Glutamic acid residue and creates a premature Stop codon at position 9 of the new reading frame, denoted p.Gly336GlufsX9. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.1005delT variant is not observed in large population cohorts (Lek et al., 2016). Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. |
| Labcorp Genetics |
RCV001860601 | SCV002219632 | pathogenic | Cholestanol storage disease | 2024-04-29 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gly336Glufs*9) 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 not present in population databases (gnomAD no frequency). 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: 817967). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001860601 | SCV004037759 | pathogenic | Cholestanol storage disease | 2023-08-30 | criteria provided, single submitter | clinical testing | Variant summary: CYP27A1 c.1005delT (p.Gly336GlufsX9) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 250090 control chromosomes. To our knowledge, no occurrence of c.1005delT in individuals affected with Cerebrotendinous Xanthomatosis and no experimental evidence demonstrating its impact on protein function have been reported. Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Prevention |
RCV003413800 | SCV004106674 | likely pathogenic | CYP27A1-related disorder | 2023-08-01 | criteria provided, single submitter | clinical testing | The CYP27A1 c.1005delT variant is predicted to result in a frameshift and premature protein termination (p.Ala335Alafs*10). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Frameshift variants in CYP27A1 are expected to be pathogenic. This variant is interpreted as likely pathogenic. |
| Baylor Genetics | RCV001860601 | SCV004192685 | likely pathogenic | Cholestanol storage disease | 2024-02-04 | criteria provided, single submitter | clinical testing |