Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002426625 | SCV002744259 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-05-22 | criteria provided, single submitter | clinical testing | The p.S837* pathogenic mutation (also known as c.2510C>G), located in coding exon 15 of the APC gene, results from a C to G substitution at nucleotide position 2510. This changes the amino acid from a serine to a stop codon within coding exon 15. This alteration occurs at the 3' terminus of theAPC gene, is not expected to trigger nonsense-mediated mRNA decay. However, premature stop codons are typically deleterious in nature and the impacted region is critical for protein function and a significant portion of the protein is affected (Ambry internal data). This mutation has been reported in multiple individuals with familial adenomatous polyposis (FAP) (Wu G et al. Genet Test, 2001;5:281-90; Borosenko V et al. Anticancer Res, 2009 Feb;29:711-5; Liu Q et al. Tumour Biol, 2016 Aug;37:11421-7). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
| Invitae | RCV003534325 | SCV004293625 | pathogenic | Familial adenomatous polyposis 1 | 2023-12-28 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser837*) in the APC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 2007 amino acid(s) of the APC protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with familial adenomatous polyposis (PMID: 11960572, 19331226). ClinVar contains an entry for this variant (Variation ID: 82631). 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. A different truncation (p.Tyr2645Lysfs*14) that lies downstream of this variant has been determined to be pathogenic (PMID: 9824584, 1316610, 27081525, 8381579, 22135120, Invitae). This suggests that deletion of this region of the APC protein is causative of disease. For these reasons, this variant has been classified as Pathogenic. |
| Systems Biology Platform Zhejiang California International Nano |
RCV000073620 | SCV000105211 | cancer | Familial colorectal cancer | no assertion criteria provided | not provided | Converted during submission to other. |