Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003772991 | SCV002253689 | uncertain significance | Familial adenomatous polyposis 1 | 2023-10-10 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 2195 of the APC protein (p.Tyr2195Phe). 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: 1464317). 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. 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 | RCV004044518 | SCV005033868 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-02-04 | criteria provided, single submitter | clinical testing | The p.Y2195F variant (also known as c.6584A>T), located in coding exon 15 of the APC gene, results from an A to T substitution at nucleotide position 6584. The tyrosine at codon 2195 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Based on the available evidence, the clinical significance of this alteration remains unclear. |