Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003336295 | SCV001219969 | pathogenic | Familial adenomatous polyposis 1 | 2023-10-04 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp423*) 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). 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: 10094547, 23159591). ClinVar contains an entry for this variant (Variation ID: 851219). For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV002374927 | SCV002687870 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-02-05 | criteria provided, single submitter | clinical testing | The p.W423* pathogenic mutation (also known as c.1268G>A), located in coding exon 9 of the APC gene, results from a G to A substitution at nucleotide position 1268. This changes the amino acid from a tryptophan to a stop codon within coding exon 9. This pathogenic variant has been reported in numerous individuals and families diagnosed with FAP or AFAP (Staninova-Stojovska M et al. Balkan J Med Genet. 2019 Dec;22:5-16; Kerr SE et al. J Mol Diagn. 2013 Jan;15:31-43; Friedl W et al. Hered Cancer Clin Pract. 2005 Sep;3:95-114; Giarola M et al. Hum Mutat. 1999;13:116-23; Ambry internal data). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). 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. |
Gene |
RCV003106107 | SCV003762087 | pathogenic | not provided | 2022-06-30 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 10094547, 23159591) |
Myriad Genetics, |
RCV003336295 | SCV004044789 | pathogenic | Familial adenomatous polyposis 1 | 2023-05-01 | 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. |