Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000506699 | SCV000602531 | pathogenic | not specified | 2017-01-13 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV003335440 | SCV000768147 | pathogenic | Familial adenomatous polyposis 1 | 2021-03-29 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 5 of the APC gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in APC are known to be pathogenic (PMID: 17963004, 20685668). Experimental studies using patient-derived RNA have suggested that this variant causes aberrant splicing, but the data was not shown in the literature (PMID: 9950360). This variant has been reported in individuals affected with familial adenomatous polyposis (PMID: 9950360, 20685668). ClinVar contains an entry for this variant (Variation ID: 439410). This variant is not present in population databases (ExAC no frequency). |
| Ambry Genetics | RCV002350126 | SCV002643156 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-06-30 | criteria provided, single submitter | clinical testing | The c.532-1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide upstream from coding exon 5 of the APC gene. This alteration has been observed in individuals with a personal and/or family history that is consistent with APC-related disease (Wallis YL et al. J Med Genet, 1999 Jan;36:14-20; Lagarde A et al. J Med Genet, 2010 Oct;47:721-2; Ambry internal data). RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Myriad Genetics, |
RCV003335440 | SCV004045498 | likely pathogenic | Familial adenomatous polyposis 1 | 2023-04-26 | 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. |
| Baylor Genetics | RCV002527346 | SCV004200820 | pathogenic | Familial adenomatous polyposis 1 | 2023-08-01 | criteria provided, single submitter | clinical testing |