Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000491636 | SCV000579811 | pathogenic | Hereditary cancer-predisposing syndrome | 2018-07-17 | criteria provided, single submitter | clinical testing | The p.S713* pathogenic mutation (also known as c.2138C>G), located in coding exon 15 of the APC gene, results from a C to G substitution at nucleotide position 2138. This changes the amino acid from a serine to a stop codon within coding exon 15. This alteration has been described in numerous individuals with adenomatous polyposis in the literature (Giarola M et al. Hum. Mutat. 1999; 13:116-23, Miyoshi Y et al. Proc. Natl. Acad. Sci. U.S.A. 1992; 89:4452-6, Nishisho I et al. Science 1991; 253:665-9). One such individual also had mandibular osteomas, consistent with the Gardner syndrome phenotype included in the FAP spectrum (Nishisho I et al. Science 1991; 253:665-9). In addition to the clinical data presented in the literature, 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. |
| Invitae | RCV003337226 | SCV002240068 | pathogenic | Familial adenomatous polyposis 1 | 2021-09-29 | criteria provided, single submitter | clinical testing | 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. ClinVar contains an entry for this variant (Variation ID: 800). This premature translational stop signal has been observed in individual(s) with clinical features of APC-related conditions (PMID: 1651563, 30897307). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ser713*) in the APC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 2131 amino acid(s) of the APC protein. |
| Myriad Genetics, |
RCV003337226 | SCV004044016 | pathogenic | Familial adenomatous polyposis 1 | 2023-05-04 | 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. |
| OMIM | RCV000000837 | SCV000020987 | pathogenic | Gardner syndrome | 1991-08-09 | no assertion criteria provided | literature only |