Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003764835 | SCV001495809 | uncertain significance | Familial adenomatous polyposis 1 | 2025-01-14 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 2252 of the APC protein (p.Pro2252Ala). This variant is present in population databases (rs587778035, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 133520). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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. |
| Center for Genomic Medicine, |
RCV000120027 | SCV004025084 | likely benign | not specified | 2025-03-04 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000120027 | SCV005076987 | uncertain significance | not specified | 2024-04-23 | criteria provided, single submitter | clinical testing | Variant summary: APC c.6754C>G (p.Pro2252Ala) results in a non-conservative amino acid change located in the Adenomatous polyposis coli protein basic domain (IPR009234) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 250950 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.6754C>G has been reported in the literature in individuals affected with primary hyperparathyroidism and Biliary tract cancer, without strong evidence for causality (example, Okawa_2023, Park_2022). These report(s) do not provide unequivocal conclusions about association of the variant with Colorectal Cancer Risk. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 36243179, 35586626). ClinVar contains an entry for this variant (Variation ID: 133520). Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Ambry Genetics | RCV005384653 | SCV006038972 | benign | Hereditary cancer-predisposing syndrome | 2025-01-31 | criteria provided, single submitter | clinical testing | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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. |
| ITMI | RCV000120027 | SCV000084158 | not provided | not specified | 2013-09-19 | no assertion provided | reference population |