Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV000583549 | SCV000686819 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2019-08-22 | criteria provided, single submitter | clinical testing | This variant causes a T>C nucleotide substitution at the +2 position of intron 2 of the APC gene. Splice site prediction tools predict that this variant may have a significant impact on RNA splicing. Although this prediction has not been confirmed in published RNA studies, this variant is expected to result in an absent or disrupted protein product. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of APC function is a known mechanism of disease. Based on the available evidence, this variant is classified as Likely Pathogenic. |
| Myriad Genetics, |
RCV003337320 | SCV004043278 | likely pathogenic | Familial adenomatous polyposis 1 | 2023-04-24 | 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. |
| Invitae | RCV003337320 | SCV004306545 | likely pathogenic | Familial adenomatous polyposis 1 | 2023-07-30 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with APC-related conditions. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Studies have shown that disruption of this splice site results in activation of a cryptic splice site and introduces a premature termination codon (Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. ClinVar contains an entry for this variant (Variation ID: 490194). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 2 of the APC gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. |
| ARUP Laboratories, |
RCV000582751 | SCV004563328 | likely pathogenic | not provided | 2023-02-27 | criteria provided, single submitter | clinical testing | The APC c.135+2T>C variant (rs1554067164), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 490194). This variant is also absent from the Genome Aggregation Database, indicating it is not a common polymorphism. This variant disrupts the canonical splice donor site of intron 1, which is likely to negatively impact gene function. Based on available information, this variant is considered to be likely pathogenic. |
| Mayo Clinic Laboratories, |
RCV000582751 | SCV000691701 | likely pathogenic | not provided | no assertion criteria provided | clinical testing |