ClinVar Miner

Submissions for variant NC_000005.10:g.(?_112775623)_(112844132_?)del

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000527737 SCV000647152 pathogenic Familial adenomatous polyposis 1 2018-01-27 criteria provided, single submitter clinical testing This variant is a gross deletion of the genomic region encompassing exons 5-16 of the APC gene. The 5' boundary is likely confined to intron 4. The 3' end of this event is unknown as it extends through the termination codon beyond the assayed region for this gene and may encompass additional genes. While this deletion is not anticipated to result in nonsense mediated decay, it is expected to create a truncated protein product or disrupt mRNA translation. This variant has been reported to segregate with in a family affected with adenomatous polyposis (PMID: 27391059). This variant removes, among others, the Basic Domain, the EB1 Binding Site, and the HDLG Binding Site of the APC protein, which mediate interactions with the cytoskeleton (PMID: 15311282, 17293347). While functional studies have not been performed to directly test the effect of this variant on APC protein function, a different truncating variant, c.7932_7935del (p.Tyr2645Lysfs*14), that only removes the EB1 and HDLG binding sites has been reported in several individuals with familial adenomatous polyposis (FAP) and attenuated FAP (PMID: 1316610, 8381579, 9824584, 22135120). These observations suggest that the C-terminal portion of the protein is clinically important. For these reasons, this variant has been classified as Pathogenic.
Invitae RCV001853710 SCV002243625 pathogenic Familial adenomatous polyposis 1 2021-08-12 criteria provided, single submitter clinical testing This variant is a gross deletion of the genomic region encompassing exon(s) 5-16 of the APC gene, which includes the termination codon. This deletion extends beyond the assayed region for this gene and therefore may encompass additional genes. While this deletion is not anticipated to lead to nonsense mediated decay, it is expected to alter mRNA translation or result in a truncated protein product. A similar copy number variant has been observed in individual(s) with adenomatous polyposis (PMID: 27391059). It has also been observed to segregate with disease in related individuals. This variant disrupts a region of the APC protein in which other variant(s) (p.Tyr2645Lysfs*14) have been determined to be pathogenic (PMID: 1316610, 8381579, 9824584, 22135120, 27081525; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.