Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000115103 | SCV000149012 | pathogenic | not provided | 2021-10-26 | criteria provided, single submitter | clinical testing | Intronic +5 splice site variant in a gene for which loss-of-function is a known mechanism of disease, and splice predictors support a deleterious effect; Not observed at significant frequency in large population cohorts (Lek 2016); Also known as IVS4+5G>A; This variant is associated with the following publications: (PMID: 25980754, 21813337, 26681312) |
Ambry Genetics | RCV002345412 | SCV002647231 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-12-29 | criteria provided, single submitter | clinical testing | The c.531+5G>A intronic pathogenic mutation results from a G to A substitution 5 nucleotides after coding exon 4 in the APC gene. This alteration has been observed in multiple individuals with a personal and/or family history that is consistent with APC-related disease (Ambry internal data; Susswein LR et al. Genet Med. 2016 Aug;18:823-32). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
Myriad Genetics, |
RCV003337233 | SCV004044676 | pathogenic | Familial adenomatous polyposis 1 | 2023-04-27 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. mRNA analysis has demonstrated abnormal mRNA splicing occurs [PMID: 12010888]. |