Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000255289 | SCV000322201 | likely pathogenic | not provided | 2016-03-18 | criteria provided, single submitter | clinical testing | This variant is denoted APC c.1409-6A>G or IVS11-6A>G and consists of an A>G nucleotide substitution at the -6 position of intron 11 of the APC gene. This variant is predicted to result in the gain of a new cryptic splice acceptor site five nucleotides upstream of the natural site. This variant, also reported as APC IVS10-6A>G, has been demonstrated by protein truncation testing and minigene assays to cause abnormal splicing (Cao 2000, Lagarde 2010, Grandval 2014). Cao et al. (2000) described an APC c.1409-6A>G family with 100s to 1000s of colorectal polyps, congenital hypertrophy of the retinal pigment epithelium (CHRPE) and osteoma. APC c.1409-6A>G was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. The adenine (A) nucleotide that is altered is not conserved across species. Based on currently available information, we consider APC c.1409-6A>G to be a likely pathogenic variant. |
| Myriad Genetics, |
RCV003335292 | SCV004044667 | likely pathogenic | Familial adenomatous polyposis 1 | 2023-05-01 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function. |