Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000222733 | SCV000276417 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-25 | criteria provided, single submitter | clinical testing | The p.R2530Q variant (also known as c.7589G>A), located in coding exon 15 of the APC gene, results from a G to A substitution at nucleotide position 7589. The arginine at codon 2530 is replaced by glutamine, an amino acid with highly similar properties. This alteration has been reported in a cohort of 488 patients with stages I to III breast cancer who were tested with a 25-gene panel test (Tung N et al. J. Clin. Oncol., 2016 May;34:1460-8). This alteration was observed in a Japanese population cohort of 2049 individuals who underwent whole-genome sequencing (Yamaguchi-Kabata Y et al. J Hum Genet, 2018 Feb;63:213-230). This variant has also been identified in healthy cohorts without a known history of cancer (Bodian DL et al. PLoS One, 2014 Apr;9:e94554; Akcay IM et al. Int J Cancer, 2021 01;148:285-295).This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000120044 | SCV000600155 | uncertain significance | not specified | 2017-03-15 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000222733 | SCV000681880 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-08 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with glutamine at codon 2530 of the APC protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on protein structure and function. 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 been reported in an individual affected with breast cancer (PMID: 26976419), but also in healthy control individuals (PMID: 24728327, 29192238, 32658311). This variant has also been identified in 1/250692 chromosomes 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. |
| Invitae | RCV003650379 | SCV001491555 | uncertain significance | Familial adenomatous polyposis 1 | 2023-12-01 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 2530 of the APC protein (p.Arg2530Gln). This variant is present in population databases (rs587778043, gnomAD 0.003%). This missense change has been observed in individual(s) with breast cancer (PMID: 26976419). ClinVar contains an entry for this variant (Variation ID: 133534). 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 with a negative predictive value of 95%. 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. |
| ITMI | RCV000120044 | SCV000084178 | not provided | not specified | 2013-09-19 | no assertion provided | reference population |