Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001192059 | SCV001360004 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-12-05 | criteria provided, single submitter | clinical testing | This missense variant replaces leucine with phenylalanine at codon 529 of the APC protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Labcorp Genetics |
RCV003770173 | SCV004628742 | uncertain significance | Familial adenomatous polyposis 1 | 2022-12-23 | 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: 928283). 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 leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 529 of the APC protein (p.Leu529Phe). |
| Ambry Genetics | RCV001192059 | SCV005454368 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-09-12 | criteria provided, single submitter | clinical testing | The p.L529F variant (also known as c.1585C>T), located in coding exon 12 of the APC gene, results from a C to T substitution at nucleotide position 1585. The leucine at codon 529 is replaced by phenylalanine, an amino acid with highly similar properties. This variant was detected in a cohort of 224 patients who were received for MMR and/or FAP gene molecular testing (Rey JM et al. J Mol Diagn, 2017 Jul;19:589-601). This amino acid position is well conserved in available vertebrate species. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Missense alterations in APC are not a common cause of disease (Spier I et al. Genet Med. 2024 Feb;26(2):100992). Based on the available evidence, the clinical significance of this variant remains unclear. |
| Fulgent Genetics, |
RCV005036442 | SCV005667828 | uncertain significance | Desmoid disease, hereditary; Familial adenomatous polyposis 1; Hepatocellular carcinoma; Gastric cancer; Colorectal cancer; Gastric adenocarcinoma and proximal polyposis of the stomach | 2024-02-16 | criteria provided, single submitter | clinical testing |