Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003743760 | SCV002206680 | pathogenic | Familial adenomatous polyposis 1 | 2022-08-03 | 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: 433597). 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.Leu68*) 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). |
| Myriad Genetics, |
RCV003335409 | SCV004043152 | pathogenic | Familial adenomatous polyposis 1 | 2023-04-25 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. |
| Department of Pathology and Laboratory Medicine, |
RCV000501918 | SCV000591017 | pathogenic | Carcinoma of colon | no assertion criteria provided | clinical testing | The APC p p.Leu68X variant was not identified in the literature, nor was it identified in the dbSNP, NHLBI Exome Sequencing Project (Exome Variant Server), Exome Aggregation Consortium (ExAC), HGMD, COSMIC, MutDB, InSiGHT Colon Cancer Gene Variant Database, “Zhejiang Colon Cancer Database”, ClinVar, GeneInsight VariantWire or UMD. The p.Leu68X variant leads to a premature stop codon at position 68, which is predicted to lead to a truncated or absent protein and loss of function. Loss of function variants of the APC gene are an established mechanism of disease in FAP and this is the type of variant expected to cause the disorder. This alteration would typically be predicted to result in a truncated or absent protein and loss of function; however, one study has demonstrated that for APC mutations closer to the 5’ terminus, an internal ribosome entry site is utilized to initiate translation at codon 184, resulting in a partially functional N-terminally truncated protein, which results in an attenuated phenotype (Heppner Goss 2002). In summary, based on the above information, this variant meets our laboratory’s criteria to be classified as pathogenic. |