Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002526449 | SCV000552597 | uncertain significance | Familial adenomatous polyposis 1 | 2024-12-15 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with threonine, which is neutral and polar, at codon 1958 of the APC protein (p.Asn1958Thr). This variant is present in population databases (no rsID available, gnomAD 0.007%). 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: 411440). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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. |
Gene |
RCV001775816 | SCV002012636 | uncertain significance | not provided | 2019-11-05 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Sema4, |
RCV002256270 | SCV002528054 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-20 | criteria provided, single submitter | curation | |
Ambry Genetics | RCV002256270 | SCV002651787 | uncertain significance | Hereditary cancer-predisposing syndrome | 2025-01-23 | criteria provided, single submitter | clinical testing | The p.N1958T variant (also known as c.5873A>C), located in coding exon 15 of the APC gene, results from an A to C substitution at nucleotide position 5873. The asparagine at codon 1958 is replaced by threonine, an amino acid with similar properties. This amino acid position is well 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. |
Baylor Genetics | RCV002526449 | SCV004198126 | uncertain significance | Familial adenomatous polyposis 1 | 2023-10-17 | criteria provided, single submitter | clinical testing |