Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000491236 | SCV000579810 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-03-02 | criteria provided, single submitter | clinical testing | The c.1229dupT pathogenic mutation, located in coding exon 9 of the APC gene, results from a duplication of T at nucleotide position 1229, causing a translational frameshift with a predicted alternate stop codon (p.L410Ffs*9). This alteration has been observed in at least one individual with a personal and/or family history that is consistent with APC-related disease (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Labcorp Genetics |
RCV004562410 | SCV000820269 | pathogenic | Familial adenomatous polyposis 1 | 2022-08-08 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 217919). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu410Phefs*9) in the APC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in APC are known to be pathogenic (PMID: 17963004, 20685668). |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000202239 | SCV002774305 | pathogenic | not provided | 2021-09-01 | criteria provided, single submitter | clinical testing | This frameshift variant causes the premature termination of APC protein synthesis. To the best of our knowledge, the variant has not been reported in the published literature. Based on the available information, this variant is classified as pathogenic. |
| Myriad Genetics, |
RCV004562410 | SCV004045491 | pathogenic | Familial adenomatous polyposis 1 | 2023-04-28 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
| ARUP Laboratories, |
RCV000202239 | SCV004562635 | likely pathogenic | not provided | 2023-09-14 | criteria provided, single submitter | clinical testing | The APC c.1229dup; p.Leu410PhefsTer9 variant (rs863225308), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 217919). This variant is also absent from the Genome Aggregation Database, indicating it is not a common polymorphism. This variant causes a frameshift by inserting a single nucleotide, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be likely pathogenic. |
| Mayo Clinic Laboratories, |
RCV000202239 | SCV000256911 | likely pathogenic | not provided | no assertion criteria provided | research |