Total submissions: 15
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000679068 | SCV000149013 | uncertain significance | not provided | 2022-06-06 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Observed in individuals with a Lynch syndrome-associated cancer and/or colon polyps (Hadjisavvas 2006, Yurgelun 2015); This variant is associated with the following publications: (PMID: 25980754, 16650078, 21859464, 25637381, 31159747, 18199528) |
Invitae | RCV003650372 | SCV000254025 | likely benign | Familial adenomatous polyposis 1 | 2024-01-15 | criteria provided, single submitter | clinical testing | |
Genomic Diagnostic Laboratory, |
RCV000202997 | SCV000257787 | uncertain significance | Familial multiple polyposis syndrome | 2015-02-13 | criteria provided, single submitter | clinical testing | |
Laboratory for Molecular Medicine, |
RCV000115104 | SCV000538302 | uncertain significance | not specified | 2016-06-23 | criteria provided, single submitter | clinical testing | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Only reported in 1 or 2 probands; ClinVar: 4 VUS |
Ambry Genetics | RCV000572635 | SCV000667335 | benign | Hereditary cancer-predisposing syndrome | 2021-03-31 | criteria provided, single submitter | clinical testing | This alteration is classified as 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. |
Color Diagnostics, |
RCV000572635 | SCV000681748 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-01 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with leucine at codon 1843 of the APC protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with breast cancer (PMID: 28828701), adenomatous polyposis and colon cancer (PMID: 16650078), colorectal cancer (PMID: 26508446), and another individual with a monoallelic pathogenic MUTYH variant who is suspected of Lynch syndrome (PMID: 25980754). This variant has also been identified in 21/251006 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. |
Eurofins Ntd Llc |
RCV000679068 | SCV000702013 | uncertain significance | not provided | 2016-10-24 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000148372 | SCV000785043 | uncertain significance | Familial adenomatous polyposis 1 | 2017-03-21 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV000679068 | SCV000805436 | uncertain significance | not provided | 2017-11-15 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000572635 | SCV000821817 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-08-01 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000115104 | SCV000916458 | uncertain significance | not specified | 2019-05-23 | criteria provided, single submitter | clinical testing | Variant summary: APC c.5528C>T (p.Pro1843Leu) results in a non-conservative amino acid change located in the Adenomatous polyposis coli protein repeat region 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 8.4e-05 in 251106 control chromosomes, predominantly at a frequency of 0.00019 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 3-folds higher than 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 is a benign polymorphism found primarily in populations of Non-Finnish European origin. c.5528C>T has been reported in the literature in individuals affected with Familial Adenomatous Polyposis, Colorectal cancer, Lynch syndrome and HBOC (Hadjisavvas_2006, Yurgelun_2015, Lupini_2015, Zidan_2017). These report(s) 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. Ten 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 VUS - possibly benign. |
Institute for Clinical Genetics, |
RCV000679068 | SCV002010869 | uncertain significance | not provided | 2021-11-03 | criteria provided, single submitter | clinical testing | |
Laboratory of Medical Genetics Unit, |
RCV003315229 | SCV004012961 | uncertain significance | Diffuse midline glioma, H3 K27-altered | 2022-12-09 | criteria provided, single submitter | research | |
Myriad Genetics, |
RCV000148372 | SCV004018809 | uncertain significance | Familial adenomatous polyposis 1 | 2023-02-22 | 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. |
CSER _CC_NCGL, |
RCV000148372 | SCV000190066 | uncertain significance | Familial adenomatous polyposis 1 | 2014-06-01 | no assertion criteria provided | research |