Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV004561892 | SCV000940751 | uncertain significance | Familial adenomatous polyposis 1 | 2022-03-13 | 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. This sequence change replaces asparagine, which is neutral and polar, with threonine, which is neutral and polar, at codon 1118 of the APC protein (p.Asn1118Thr). This variant is present in population databases (rs752011683, gnomAD 0.006%). 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: 646667). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. |
All of Us Research Program, |
RCV004001639 | SCV004839800 | uncertain significance | Classic or attenuated familial adenomatous polyposis | 2023-04-03 | criteria provided, single submitter | clinical testing | This missense variant replaces asparagine with threonine at codon 1118 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 2/250532 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. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV004997344 | SCV005624244 | uncertain significance | not provided | 2024-03-06 | criteria provided, single submitter | clinical testing | The APC c.3353A>C (p.Asn1118Thr) variant has not been reported in individuals with APC-related conditions in the published literature. The frequency of this variant in the general population, 0.000008 (2/250532 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the 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. |