Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV004580496 | SCV005063027 | likely pathogenic | Familial adenomatous polyposis 1 | 2022-07-19 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with APC-related conditions. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. There are several predicted outcomes of this tandem duplication on APC protein function. While APC expression may occur in the duplicated region containing promoter 1A, it is more likely to be expressed from the original region also containing promoter 1B, which has been shown to drive higher levels of APC expression (PMID: 21643010). Therefore, the duplicated copy likely results in an absent or disrupted protein product. Experimental studies have not been tested for this variant. This variant results in a copy number gain of the genomic region encompassing promoter 1A, exons 2-7, and the first 32 nucleotides of exon 8 of the APC gene (c.-1843_761dup). The duplicated copy of this region is in tandem This region includes the initiator codon of the gene. This copy number gain extends beyond the assayed region for this gene and therefore may encompass additional genes. As the precise location of this event is unknown, it may be in tandem or it may be located elsewhere in the genome. |