Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000215115 | SCV000276080 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-10-26 | criteria provided, single submitter | clinical testing | The p.Q625* pathogenic mutation (also known as c.1873C>T), located in coding exon 14 of the APC gene, results from a C to T substitution at nucleotide position 1873. This changes the amino acid from a glutamine to a stop codon within coding exon 14. This mutation has been reported in several unrelated families diagnosed with FAP (Kerr SE et al. J Mol Diagn, 2013 Jan;15:31-43; Miyoshi Y et al. Proc. Natl. Acad. Sci. U.S.A., 1992 May;89:4452-6; Wallis YL et al. J. Med. Genet., 1999 Jan;36:14-20; Cruz-Correa M et al. Fam. Cancer, 2013 Sep;12:555-62; Truta B et al. Fam. Cancer, 2005;4:127-33). In addition to the clinical information provided 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 |
RCV000520225 | SCV000617337 | 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: 28073006, 1316610, 9950360, 28576136, 28127413, 23460355, 23159591, 15951963, 25525159, 20808249) |
Invitae | RCV003337256 | SCV001226096 | pathogenic | Familial adenomatous polyposis 1 | 2023-12-24 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln625*) 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: 1316610, 15951963, 23460355). ClinVar contains an entry for this variant (Variation ID: 232045). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001194208 | SCV001363558 | pathogenic | Familial multiple polyposis syndrome | 2019-06-24 | criteria provided, single submitter | clinical testing | Variant summary: APC c.1873C>T (p.Gln625X) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251366 control chromosomes. c.1873C>T has been reported in the literature in multiple individuals affected with Familial Adenomatous Polyposis (Miyoshi_1992, Truta_2005, Wallis_1999, Kerr_2013, Cruz-Correa_2013). 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. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000520225 | SCV001469902 | pathogenic | not provided | 2019-10-28 | criteria provided, single submitter | clinical testing | The variant creates a premature nonsense codon, and is therefore predicted to result in the loss of a functional protein. Found in at least one patient with expected phenotype for this gene, and not found in general population data. |
Myriad Genetics, |
RCV003337256 | SCV004044704 | pathogenic | Familial adenomatous polyposis 1 | 2023-05-03 | 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. |