Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002523358 | SCV000552482 | uncertain significance | Familial adenomatous polyposis 1 | 2023-03-23 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 411360). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is present in population databases (rs767741687, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 71 of the APC protein (p.Arg71Ser). |
| Ambry Genetics | RCV000569830 | SCV000667337 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-01 | criteria provided, single submitter | clinical testing | The p.R71S variant (also known as c.211C>A), located in coding exon 2 of the APC gene, results from a C to A substitution at nucleotide position 211. The arginine at codon 71 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000759423 | SCV000888733 | uncertain significance | not provided | 2018-06-22 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000779735 | SCV000916503 | uncertain significance | not specified | 2018-07-19 | criteria provided, single submitter | clinical testing | Variant summary: APC c.211C>A (p.Arg71Ser) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8.3e-06 in 120868 control chromosomes (ExAC). 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.211C>A in individuals affected with Familial Adenomatous Polyposis and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and both of them classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Color Diagnostics, |
RCV000569830 | SCV001353780 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-10-31 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with serine at codon 71 of the APC protein. Computational prediction tool suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold ≤0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/250846 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. |