Total submissions: 12
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003534489 | SCV000259432 | uncertain significance | Familial adenomatous polyposis 1 | 2024-01-29 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 32 of the APC protein (p.Asn32Ser). This variant is present in population databases (rs539108537, gnomAD 0.02%). This missense change has been observed in individual(s) with breast cancer and colon cancer (PMID: 26976419, 29237405). ClinVar contains an entry for this variant (Variation ID: 218010). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt APC protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Gene |
RCV000656743 | SCV000292446 | uncertain significance | not provided | 2023-11-07 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Observed in individuals with colorectal or breast cancer, and also in controls in a case-control study of biliary tract cancer (PMID: 18199528, 26976419, 29237405, 32658311, 36243179); This variant is associated with the following publications: (PMID: 29237405, 26976419, 26900293, 27908614, 32658311, 18199528, 36243179) |
Ambry Genetics | RCV000569857 | SCV000667217 | likely benign | Hereditary cancer-predisposing syndrome | 2022-06-07 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000656743 | SCV000887557 | uncertain significance | not provided | 2018-11-05 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000569857 | SCV000910900 | likely benign | Hereditary cancer-predisposing syndrome | 2016-06-16 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000202147 | SCV000916487 | uncertain significance | not specified | 2021-02-05 | criteria provided, single submitter | clinical testing | Variant summary: APC c.95A>G (p.Asn32Ser) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 7.9e-05 in 252236 control chromosomes (gnomAD and Akcay_2020). The observed variant frequency is approximately equal to the estimated maximal expected allele frequency for a pathogenic variant in APC causing Familial Adenomatous Polyposis phenotype (7.1e-05), strongly suggesting that the variant may be benign. The variant has been found as a germline and somatic variant in patients with various cancers including but not limited to colorectal cancer, non-small cell lung cancer, and breast cancer without strong evidence for or against pathogenicity (example: Chang_2016, Lv_2017, Tung_2016, Lee_2017, Akcay_2020). These reports however, do not provide unequivocal conclusions about association of the variant with Familial Adenomatous Polyposis. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Seven other ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (n=2) or likely benign (n=1). Based on the evidence outlined above, the variant was classified as VUS-possibly benign. |
Mendelics | RCV000204603 | SCV001136868 | uncertain significance | Familial adenomatous polyposis 1 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Institute for Clinical Genetics, |
RCV000656743 | SCV002010852 | uncertain significance | not provided | 2021-11-03 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000569857 | SCV002529596 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-28 | criteria provided, single submitter | curation | |
Center for Genomic Medicine, |
RCV000202147 | SCV004243222 | likely benign | not specified | 2024-02-06 | criteria provided, single submitter | clinical testing | |
Mayo Clinic Laboratories, |
RCV000202147 | SCV000257039 | uncertain significance | not specified | no assertion criteria provided | research | ||
3DMed Clinical Laboratory Inc | RCV000677775 | SCV000803931 | uncertain significance | Neoplasm of stomach | 2018-01-25 | no assertion criteria provided | clinical testing |