Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000573010 | SCV000672539 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-07-02 | criteria provided, single submitter | clinical testing | The p.I638V variant (also known as c.1912A>G), located in coding exon 14 of the APC gene, results from an A to G substitution at nucleotide position 1912. The isoleucine at codon 638 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Missense alterations in APC are not a common cause of disease (Spier I et al. Genet Med. 2024 Feb;26(2):100992). Based on the available evidence, the clinical significance of this variant remains unclear. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001192945 | SCV001361419 | uncertain significance | not specified | 2019-05-17 | criteria provided, single submitter | clinical testing | Variant summary: APC c.1912A>G (p.Ile638Val) results in a conservative amino acid change located in the Armadillo domain of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251278 control chromosomes. 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.1912A>G in individuals affected with Familial Adenomatous Polyposis and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Labcorp Genetics |
RCV004562240 | SCV002235860 | uncertain significance | Familial adenomatous polyposis 1 | 2024-08-13 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 638 of the APC protein (p.Ile638Val). This variant is not present in population databases (gnomAD no frequency). 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: 83212). 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. |
| Systems Biology Platform Zhejiang California International Nano |
RCV000074203 | SCV000105796 | cancer | Familial colorectal cancer | no assertion criteria provided | not provided | Converted during submission to other. |