Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003744664 | SCV000957900 | uncertain significance | Familial adenomatous polyposis 1 | 2023-02-25 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 852 of the APC protein (p.Leu852Trp). This variant is present in population databases (no rsID available, gnomAD 0.002%). 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: 660204). 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 | RCV001015946 | SCV001176841 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-16 | criteria provided, single submitter | clinical testing | The p.L852W variant (also known as c.2555T>G), located in coding exon 15 of the APC gene, results from a T to G substitution at nucleotide position 2555. The leucine at codon 852 is replaced by tryptophan, an amino acid with similar properties. This amino acid position is well 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. |
| Illumina Laboratory Services, |
RCV001157042 | SCV001318588 | uncertain significance | APC-Associated Polyposis Disorders | 2017-04-28 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |