Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000162741 | SCV000213213 | pathogenic | Hereditary cancer-predisposing syndrome | 2018-02-23 | criteria provided, single submitter | clinical testing | The c.5757delT pathogenic mutation, located in coding exon 15 of the APC gene, results from a deletion of one nucleotide at nucleotide position 5757, causing a translational frameshift with a predicted alternate stop codon (p.R1920Efs*50). This alteration was previously seen in a 53-year-old patient with polyposis (Foley SB et al. EBioMedicine. 2015 Jan;2(1):74-81). In addition to the information presented in the literature, this alteration is expected to result in loss of function by premature protein truncation. As such, this alteration is interpreted as a disease-causing mutation. |
Invitae | RCV003534419 | SCV003439222 | pathogenic | Familial adenomatous polyposis 1 | 2023-04-22 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 183880). This premature translational stop signal has been observed in individual(s) with APC-related conditions (PMID: 26023681). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg1920Glufs*50) in the APC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 924 amino acid(s) of the APC protein. This variant is expected to disrupt the EB1 and HDLG binding sites, which mediate interactions with the cytoskeleton (PMID: 15311282, 17293347). While functional studies have not been performed to directly test the effect on APC protein function, this suggests that disruption of the C-terminal portion of the protein is functionally important. For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the APC protein in which other variant(s) (p.Tyr2645Lysfs*14) have been determined to be pathogenic (PMID: 1316610, 8381579, 9824584, 22135120, 27081525; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. |
Myriad Genetics, |
RCV002516443 | SCV004044690 | pathogenic | Familial adenomatous polyposis 1 | 2023-05-12 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |