Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000478593 | SCV000572248 | likely pathogenic | not provided | 2016-11-07 | criteria provided, single submitter | clinical testing | The c.939dupC variant in the CPOX gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant causes a frameshift starting with codon Lysine 314, changes this amino acid to a Glutamine residue, and creates a premature Stop codon at position 3 of the new reading frame, denoted p.Lys314GlnfsX3. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.939dupC variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.939dupC as a likely pathogenic variant. |
| Invitae | RCV000478593 | SCV004433985 | pathogenic | not provided | 2023-02-14 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Lys314Glnfs*3) in the CPOX gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CPOX are known to be pathogenic (PMID: 9888388). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CPOX-related conditions. ClinVar contains an entry for this variant (Variation ID: 422712). For these reasons, this variant has been classified as Pathogenic. |