Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002400408 | SCV002707267 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-08-29 | criteria provided, single submitter | clinical testing | The p.K533E variant (also known as c.1597A>G), located in coding exon 11 of the CTNNA1 gene, results from an A to G substitution at nucleotide position 1597. The lysine at codon 533 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. |
Labcorp Genetics |
RCV003679088 | SCV004413116 | uncertain significance | not provided | 2024-12-17 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 533 of the CTNNA1 protein (p.Lys533Glu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CTNNA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1700595). 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 CTNNA1 protein function with a negative predictive value of 80%. 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. |
Genomic Center, |
RCV002274833 | SCV002559838 | uncertain significance | Colorectal cancer | no assertion criteria provided | case-control |