Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003555878 | SCV004293134 | uncertain significance | not provided | 2023-09-19 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 6 of the CPOX gene. It does not directly change the encoded amino acid sequence of the CPOX protein. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product. This variant is present in population databases (rs370245685, gnomAD 0.005%). This variant has been observed in individual(s) with autosomal recessive harderoporphyria (PMID: 9454777). 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: 457). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 6, but is expected to preserve the integrity of the reading-frame (PMID: 9454777). 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. |
OMIM | RCV000000486 | SCV000020635 | pathogenic | Harderoporphyria | 1998-02-15 | no assertion criteria provided | literature only |