Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001032266 | SCV001195573 | uncertain significance | Familial adenomatous polyposis 1 | 2019-10-30 | criteria provided, single submitter | clinical testing | This variant results in a copy number gain of the genomic region encompassing promoter 1A of the APC gene. The 5' boundary is likely confined to be between promoter 1B and promoter 1A. The 3' boundary is likely confined to intron 1 of the APC gene. While the exact position of this variant cannot be determined from this data, sub-genic copy number gains are generally in tandem (PMID: 25640679). A copy number gain of promoter 1A alone has not been reported in the literature in individuals with APC-related conditions. Experimental studies are not available for this variant, and the functional significance of this duplication is currently unknown. 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). 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. |
| Invitae | RCV001862450 | SCV002256849 | uncertain significance | Familial adenomatous polyposis 1 | 2021-10-08 | criteria provided, single submitter | clinical testing | This variant results in a copy number gain of the genomic region encompassing promoter 1A of the APC gene. The 5' boundary is likely confined to the region between promoter 1B and promoter 1A. The 3' boundary is likely confined to intron 1 of the APC gene. While the exact position of this variant cannot be determined from this data, sub-genic copy number gains are generally in tandem (PMID: 25640679). This variant has not been reported in the literature in individuals affected with APC-related conditions. Experimental studies are not available for this variant, and the functional significance of this duplication is currently unknown. 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). 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. |