Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000202308 | SCV000617334 | pathogenic | not provided | 2017-09-12 | criteria provided, single submitter | clinical testing | This variant is denoted APC c.1409-1G>T or IVS11-1G>T and consists of a G>T nucleotide substitutionat the -1 position of intron 11 of the APC gene. This variant destroys a canonical splice acceptor site and is predicted tocause abnormal gene splicing, leading to either an abnormal message that is subject to nonsense-mediated mRNAdecay or to an abnormal protein product. This variant has been reported in at least one individual with familialadenomatous polyposis (Lagarde 2010). Based on the current evidence, we consider this variant to be pathogenic |
Ambry Genetics | RCV000570454 | SCV000675943 | pathogenic | Hereditary cancer-predisposing syndrome | 2017-07-18 | criteria provided, single submitter | clinical testing | The c.1409-1G>T intronic pathogenic mutation results from a G to T substitution one nucleotide upstream from coding exon 11 of the APC gene. This alteration was identified in 1/863 French patients with FAP. (Lagarde A et al. J. Med. Genet., 2010 Oct;47:721-2). Another alteration at this same nucleotide positiion, c.1409-1G>A, has been reported in multiple FAP families, and it has been shown to create a new acceptor splice site one base pair downstream with a lower splicing efficiency but no indication of exon skipping (Wallis YL et al. J Med Genet. 1999 Jan;36(1):14-20; Aretz S et al. Hum Mutat. 2004 Nov;24(5):370-80). In addition to the information 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 classified as pathogenic. |
Invitae | RCV003534477 | SCV001401151 | pathogenic | Familial adenomatous polyposis 1 | 2022-07-19 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Studies have shown that disruption of this splice site is associated with altered splicing resulting in multiple RNA products (Invitae). ClinVar contains an entry for this variant (Variation ID: 217927). Disruption of this splice site has been observed in individuals with familial adenomatous polyposis (PMID: 950360, 15459959, 19036155, 20685668; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 11 of the APC gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site 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). |
Myriad Genetics, |
RCV002519584 | SCV004044867 | 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. |
Mayo Clinic Laboratories, |
RCV000202308 | SCV000256920 | pathogenic | not provided | no assertion criteria provided | research |