Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000481933 | SCV000573328 | uncertain significance | not provided | 2017-02-14 | criteria provided, single submitter | clinical testing | The K2062N variant has not, to our knowledge, been published in the literature as pathogenic or benign. This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The K2062N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This variant occurs at a position that is conserved in mammals and is not located in a known functional domain. In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, we consider K2062N to be a variant of uncertain significance. |
| Invitae | RCV003535766 | SCV000947082 | uncertain significance | Familial adenomatous polyposis 1 | 2024-01-25 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 2062 of the APC protein (p.Lys2062Asn). This variant is not present in population databases (gnomAD no frequency). 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: 423610). 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 | RCV001024978 | SCV001187081 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-01-04 | criteria provided, single submitter | clinical testing | The p.K2062N variant (also known as c.6186A>C), located in coding exon 15 of the APC gene, results from an A to C substitution at nucleotide position 6186. The lysine at codon 2062 is replaced by asparagine, an amino acid with similar properties. This amino acid position is highly 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. |