Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000235631 | SCV000293917 | uncertain significance | not provided | 2017-12-12 | criteria provided, single submitter | clinical testing | This variant is denoted APC c.7922A>C at the cDNA level, p.Lys2641Thr (K2641T) at the protein level, and results in the change of a Lysine to a Threonine (AAG>ACG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Lys2641Thr was not observed in large population cohorts (Lek 2016). Since Lysine and Threonine differ in some properties, this is considered a semi-conservative amino acid substitution. APC Lys2641Thr is located in the EB1 binding domain (Azzopardi 2008). In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether APC Lys2641Thr is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
Ambry Genetics | RCV000575151 | SCV000667530 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-16 | criteria provided, single submitter | clinical testing | The p.K2641T variant (also known as c.7922A>C), located in coding exon 15 of the APC gene, results from an A to C substitution at nucleotide position 7922. The lysine at codon 2641 is replaced by threonine, 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. |
Invitae | RCV003535663 | SCV000949871 | uncertain significance | Familial adenomatous polyposis 1 | 2023-05-02 | 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: 246385). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 2641 of the APC protein (p.Lys2641Thr). |