Total submissions: 13
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000164280 | SCV000214907 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-03-30 | criteria provided, single submitter | clinical testing | The p.R332* pathogenic mutation (also known as c.994C>T), located in coding exon 9 of the APC gene, results from a C to T substitution at nucleotide position 994. This changes the amino acid from an arginine to a stop codon within coding exon 9. This mutation has been identified in many patients diagnosed with FAP or AFAP from various ethnicities (Soravia et al. Am J Hum Genet. 1998. 62:1290-1301; Gomez-Fernandez N et al. BMC Med Genet. 2009 Jun 16;10:57; Friedl W & Aretz S. Hered Cancer Clin Pract. 2005 Sep 15;3(3):95-114; Chubb D et al. J. Clin. Oncol. 2015 Feb;33(5):426-32). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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 |
RCV000202243 | SCV000292448 | pathogenic | not provided | 2021-10-26 | 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 (Lek et al., 2016); Observed in individuals with APC-related phenotypes (Soravia 1998, Andreutti-Zaugg 1999, Hutter 2001, Friedl 2005, Sieber 2006, Chubb 2015); This variant is associated with the following publications: (PMID: 28010732, 30072583, 16461775, 1646175, 11001924, 20223039, 20924072, 16134147, 17411426, 11748858, 19531215, 23159591, 25559809, 22987206, 11317365, 11960572, 19793053, 22425061, 20105204, 25525159, 9585611, 28790112, 29691710, 10094557, 31461190, 33468868, 33294277) |
Color Diagnostics, |
RCV000164280 | SCV000537665 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-12-11 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 10 of the APC gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individuals and families affected with familial adenomatous polyposis, attenuated familial adenomatous polyposis, and colorectal cancer (PMID: 9585611, 10713886, 11001924, 11748858, 11317365, 16461775, 17411426, 19531215, 20223039, 23159591, 25590978). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of APC function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |
Invitae | RCV002228714 | SCV000552518 | pathogenic | Familial adenomatous polyposis 1 | 2024-01-30 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg332*) 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 (FAP) and attenuated familial adenomatous polyposis (AFAP) (PMID: 9585611, 11748858, 17411426, 19531215, 25559809). ClinVar contains an entry for this variant (Variation ID: 184937). For these reasons, this variant has been classified as Pathogenic. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000202243 | SCV000887559 | pathogenic | not provided | 2022-12-22 | criteria provided, single submitter | clinical testing | This nonsense variant causes the premature termination of APC protein synthesis. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, the variant has been reported in individuals with familial adenomatous polyposis (FAP) (PMIDs: 19531215 (2009), 11748858 (2001), 10713886 (2000)), suspected FAP (PMID: 20223039 (2005)), attenuated FAP (PMIDs: 17411426 (2007), 9585611 (1998)), colorectal cancer (PMID: 25559809 (2015)), and Lynch-like syndrome (PMID: 33294277 (2020)). Based on the available information, this variant is classified as pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000503333 | SCV000916472 | pathogenic | Familial multiple polyposis syndrome | 2018-04-18 | criteria provided, single submitter | clinical testing | Variant summary: APC c.994C>T (p.Arg332X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 276792 control chromosomes (gnomAD). The variant, c.994C>T, has been reported in the literature in multiple individuals affected with Familial Adenomatous Polyposis (Cao_2000, Friedl_2005). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Multiple ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as "pathogenic." Based on the evidence outlined above, the variant was classified as pathogenic. |
Department of Molecular Diagnostics, |
RCV000460182 | SCV001499601 | pathogenic | Familial adenomatous polyposis 1 | 2020-04-02 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000202243 | SCV002062608 | pathogenic | not provided | 2021-11-01 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002498813 | SCV002812650 | pathogenic | Desmoid disease, hereditary; Familial adenomatous polyposis 1; Hepatocellular carcinoma; Gastric cancer; Colorectal cancer; Gastric adenocarcinoma and proximal polyposis of the stomach | 2022-01-04 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV002228714 | SCV004044662 | pathogenic | Familial adenomatous polyposis 1 | 2023-04-28 | 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. |
Mayo Clinic Laboratories, |
RCV000202243 | SCV000257040 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Department of Pathology and Laboratory Medicine, |
RCV000202243 | SCV000591061 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Genome |
RCV000202243 | SCV002818448 | not provided | not provided | no assertion provided | phenotyping only | Variant classified as Pathogenic and reported on 10-29-2021 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. |