Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000570424 | SCV000667483 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-31 | criteria provided, single submitter | clinical testing | The p.S2586I variant (also known as c.7757G>T), located in coding exon 15 of the APC gene, results from a G to T substitution at nucleotide position 7757. The serine at codon 2586 is replaced by isoleucine, an amino acid with dissimilar properties. This variant was also detected as a secondary finding in 1 out of 561 ClinSeq participants unselected for personal or family history of cancer who underwent exome sequencing, however the clinical information for this particular individual was not provided (Johnston JJ et al. Am. J. Hum. Genet., 2012 Jul;91:97-108). 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. |
| Invitae | RCV002513339 | SCV000768293 | uncertain significance | Familial adenomatous polyposis 1 | 2023-12-23 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 2586 of the APC protein (p.Ser2586Ile). 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: 41537). 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. |
| Fulgent Genetics, |
RCV002482949 | SCV002788125 | uncertain significance | Desmoid disease, hereditary; Familial adenomatous polyposis 1; Hepatocellular carcinoma; Gastric cancer; Colorectal cancer; Gastric adenocarcinoma and proximal polyposis of the stomach | 2022-04-06 | criteria provided, single submitter | clinical testing | |
| Biesecker Lab/Clinical Genomics Section, |
RCV000034422 | SCV000043141 | variant of unknown significance | not provided | 2012-07-13 | no assertion criteria provided | research | Converted during submission to Uncertain significance. |