Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003767866 | SCV000768272 | uncertain significance | Familial adenomatous polyposis 1 | 2023-07-10 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 537558). This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2038 of the APC protein (p.Leu2038Val). This variant is present in population databases (no rsID available, gnomAD 0.01%). This missense change has been observed in individual(s) with familial adenomatous polyposis (PMID: 12503191, 35189564). 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. |
| Color Diagnostics, |
RCV000773299 | SCV000906991 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-05-14 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000773299 | SCV002655466 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-15 | criteria provided, single submitter | clinical testing | The p.L2038V variant (also known as c.6112C>G), located in coding exon 15 of the APC gene, results from a C to G substitution at nucleotide position 6112. The leucine at codon 2038 is replaced by valine, an amino acid with highly similar properties. This alteration has been reported in a Japanese familial adenomatous polyposis (FAP) kindred (Nimura Y et al. Jpn J Hum Genet, 1997 Sep;42:433-9). However, based on data from gnomAD, the frequency for this variant is above the maximum credible frequency for a disease-causing variant in this gene based on internally established thresholds (Karczewski et al. Nature. 2020 May;581(7809):434-443; Whiffin et al. Genet Med. 2017 10;19:1151-1158). 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 and conflicting at this time, the clinical significance of this alteration remains unclear. |