Total submissions: 11
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000159568 | SCV000209543 | uncertain significance | not provided | 2023-02-01 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 18199528, 31980526) |
Ambry Genetics | RCV000219951 | SCV000273674 | likely benign | Hereditary cancer-predisposing syndrome | 2020-08-21 | 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. |
Counsyl | RCV000409928 | SCV000489561 | uncertain significance | Familial adenomatous polyposis 1 | 2016-10-27 | criteria provided, single submitter | clinical testing | |
Invitae | RCV003315949 | SCV000552493 | benign | Familial adenomatous polyposis 1 | 2024-01-30 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000219951 | SCV000681852 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-07 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with threonine at codon 2392 of the APC protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with APC-related disorders in the literature. This variant has been identified in 2/250282 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000159568 | SCV001133361 | uncertain significance | not provided | 2019-07-23 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001192797 | SCV001361156 | uncertain significance | not specified | 2019-04-04 | criteria provided, single submitter | clinical testing | Variant summary: APC c.7174C>A (p.Pro2392Thr) results in a non-conservative amino acid change located in the Adenomatous polyposis coli protein basic domain of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4.1e-06 in 245024 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.7174C>A in individuals affected with Familial Adenomatous Polyposis and no experimental evidence demonstrating its impact on protein function have been reported. Five ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Institute for Clinical Genetics, |
RCV000159568 | SCV002011085 | uncertain significance | not provided | 2021-11-03 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000219951 | SCV002527479 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-21 | criteria provided, single submitter | curation | |
Myriad Genetics, |
RCV003315949 | SCV004018738 | uncertain significance | Familial adenomatous polyposis 1 | 2023-02-17 | criteria provided, single submitter | clinical testing | This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk. |
Baylor Genetics | RCV000409928 | SCV004206673 | uncertain significance | Familial adenomatous polyposis 1 | 2023-04-20 | criteria provided, single submitter | clinical testing |