Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000493148 | SCV000581403 | pathogenic | Familial adenomatous polyposis 1 | 2019-12-03 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing the promoter 1B sequences of the APC gene. The 5' end of this event is unknown as it extends beyond the assayed region for this gene, and therefore may encompass additional genes. The 3' boundary is likely confined to the region between promoter 1B and promoter 1A of the APC gene (PMID: 21643010). Gross deletions of the two APC promoter regions are known to be pathogenic. Similar deletions involving only the promoter 1B region have been reported in the literature in several families affected with familial adenomatous polyposis (PMID: 25243319, 21643010, 24946964, 23725351). Allele-specific expression analysis has shown that deletions of the promoter 1B reduced APC mRNA expression in patient-derived samples (PMID: 21643010, 23725351, 25243319). For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001865533 | SCV002245978 | pathogenic | Familial adenomatous polyposis 1 | 2022-10-12 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing the promoter 1B of the APC gene. The 5' end of this event is unknown as it extends beyond the assayed region for this gene, and therefore may encompass additional genes. The 3' boundary is likely confined to the region between promoter 1B and promoter 1A of the APC gene (PMID: 21643010). This variant has been observed in individuals with familial adenomatous polyposis (PMID: 21643010, 23725351, 24946964, 25243319). Studies have shown that this variant alters APC gene expression (PMID: 21643010, 23725351, 25243319). The region of the APC gene that includes the promoter 1B has been determined to be clinically significant (PMID: 21643010, 23725351, 24946964, 25243319, 25941542). Therefore, deletions that encompass that region are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |