Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002035319 | SCV002236928 | pathogenic | Peroxisome biogenesis disorder | 2023-11-09 | criteria provided, single submitter | clinical testing | This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 15 of the PEX6 gene (c.2601_2602ins?), causing a frameshift at codon 868 (p.Val868fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PEX6-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in PEX6 are known to be pathogenic (PMID: 10408779, 21031596, 31831025). For these reasons, this variant has been classified as Pathogenic. |