Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000164870 | SCV000215555 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-12 | criteria provided, single submitter | clinical testing | The p.R1920Q variant (also known as c.5759G>A), located in coding exon 15 of the APC gene, results from a G to A substitution at nucleotide position 5759. The arginine at codon 1920 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000780843 | SCV000918450 | uncertain significance | not specified | 2018-01-22 | criteria provided, single submitter | clinical testing | Variant summary: The c.5759G>A (p.Arg1920Gln) in APC gene is a missense variant involves a mildly conserved nucleotide located within the APC_u15 - a short region of natively unstructured sequence lying between the fifth and sixth creatine-rich domains (NCBI conserved domain database). The 3/4 in silico tools used predict benign outcome for this variant, however no functional studies supporting these predictions were published at the time of evaluation. The c.5759G>A was identified in the control population dataset of gnomAD at a low frequency of 0.000004 (1/ 244648 chrs tested). The observed frequency does not exceed the maximum expected allele frequency for a pathogenic variant of 0.000074, suggesting that it is not a common polymorphism. The variant has not, to our knowledge, been reported in FAP patients via published reports, but is cited as VUS by at least one reputable database/clinical laboratory. Taken together, due to lack of supportive evidence, the variant was classified as VUS, until new information becomes available. |
| Invitae | RCV003743613 | SCV001536481 | uncertain significance | Familial adenomatous polyposis 1 | 2023-12-29 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1920 of the APC protein (p.Arg1920Gln). This variant is present in population databases (rs587780599, gnomAD 0.003%). 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: 185443). 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. |
| Color Diagnostics, |
RCV000164870 | SCV001735618 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-07 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with glutamine at codon 1920 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 2/249934 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. |