Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV000581085 | SCV000681554 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-17 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with histidine at codon 94 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 1/246238 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. |
Invitae | RCV003744579 | SCV000768109 | uncertain significance | Familial adenomatous polyposis 1 | 2024-01-22 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 94 of the APC protein (p.Arg94His). This variant is present in population databases (rs774229223, gnomAD 0.0009%). 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: 489430). 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. |
Ambry Genetics | RCV000581085 | SCV001177664 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-14 | criteria provided, single submitter | clinical testing | The p.R94H variant (also known as c.281G>A), located in coding exon 3 of the APC gene, results from a G to A substitution at nucleotide position 281. The arginine at codon 94 is replaced by histidine, 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Center for Genomic Medicine, |
RCV002268207 | SCV002550552 | uncertain significance | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | |
Gene |
RCV003318600 | SCV004022833 | uncertain significance | not provided | 2023-07-18 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in a patient with colorectal cancer (Henn et al., 2019); This variant is associated with the following publications: (PMID: 30680046) |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003318600 | SCV004221387 | uncertain significance | not provided | 2023-01-30 | criteria provided, single submitter | clinical testing | To the best of our knowledge, the variant has not been reported in the published literature. The frequency of this variant in the general population, 0.000013 (2/152118 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |
All of Us Research Program, |
RCV004001223 | SCV004841719 | uncertain significance | Classic or attenuated familial adenomatous polyposis | 2023-08-28 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with histidine at codon 94 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 1/246238 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. |