Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003337277 | SCV000552580 | pathogenic | Familial adenomatous polyposis 1 | 2022-09-01 | 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: 411429). 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.Ser5*) 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). |
Ambry Genetics | RCV001011888 | SCV001172269 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-14 | criteria provided, single submitter | clinical testing | The p.S5* variant (also known as c.14C>A), located in coding exon 1 of the APC gene, results from a C to A substitution at nucleotide position 14. This changes the amino acid from a serine to a stop codon within coding exon 1. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay; however, this alteration and others loss-of-function alterations that occur at the extreme N-terminus of APC have been observed in numerous individuals who do not have a personal or family history that is consistent with or suggestive of APC associated disease (Ambry internal data). This suggests the use of an alternate translation initiation site which could be imparted by the second, in-frame methionine located at p.M18. Evidence for the use of this methionine or the functional characteristics of an APC protein lacking amino acids 1-17 have not been published. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Myriad Genetics, |
RCV003337277 | SCV004045082 | pathogenic | Familial adenomatous polyposis 1 | 2023-04-24 | 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. |